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CD Markers
Last revised: 28 April 2013
Author: Nat Pernick, M.D., PathologyOutlines.com, Inc.
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.
See also Stains chapter
Navigational links to CD markers
General
1 1a 1b 1c 1d 1e 2 2R
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10 11 11a 11b 11c 11d 12w 13
14 15 15s 15u 16a 16b 17 18 19
20 21 22 23 24 25 26 27 28 29
30 30v 31 32 33 34 35 36 37 38 39
40 41 42a 42b 42c 42d 43 44 44R
45 45RO 45RA 45RB 45RC
46 47 47R 48 49a 49b 49c 49d 49e 49f
50 51 52 53 54 55 56 57 58 59
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Note: no/minimal information is available on CD199, CD214, CD218, CD220
Primary references
top
American Journal of Clinical Pathology
American Journal of Surgical Pathology
Archives of Pathology and Laboratory Medicine
Human Pathology
Modern Pathology
CD Marker websites: http://www.uniprot.org/docs/cdlist.txt
Websites: PathoPic, PEIR
Digital Library
Also known as ICAM-3, the third counter receptor for LFA-1 (CD54)
Provides adhesion signals important in B-T cell interactions and regulates leukocyte morphology
May predict resistance to radiation therapy in cervical cancer (Int J Cancer 2005;117:194)
Costimulator for HIV1 replication (J Virol 2004;78:6692, J Virol 2002;76:32)
Uses: no significant clinical use by pathologists
Positive staining (normal): leukocytes including eosinophils (J Allergy Clin Immunol 2003;111:1024) and mast cells (Cell Adhes Commun 1999;7:195), epidermal Langerhans cells (J Invest Dermatol 1995;104:995), endothelial cells (J Vasc Res 2004;41:28)
Positive staining (disease): synovium in rheumatoid arthritis (Arthritis Rheum 2003;48:360)
Negative staining: non-hematopoietic cells, platelets (J Clin Invest 1994;94:1243)
References: OMIM 146631
Also called integrin alpha chain V or vitronectin receptor-alpha chain
Integrins are membrane receptors for extracellular matrix-mediated cell adhesion and migration, cytoskeletal organization, cell proliferation, cell survival and differentiation
Integrins are composed of an alpha chain and a beta chain
Alpha-V integrins are a subset of integrins with a common alpha-V subunit combined with beta subunits 1, 3, 5, 6 or 8
The beta chain of the vitronectin receptor is CD61
Most alpha-V integrins recognize the RGD (Arg-Gly-Asp) sequence in various ligands such as vitronectin, fibronectin, osteopontin, bone sialoprotein, thrombospondin, fibrinogen, von Willebrand factor, tenascin or agrin
Alpha V beta 3 integrin may mediate melanoma progression (Oncogene 2005;24:4710)
CD51 on some dendritic cells serves as adenovirus receptor (J Leukoc Biol 2006;79:1271)
Uses: no significant clinical use by pathologists
Positive staining (normal): endothelial cells, megakaryocytes, osteoclasts (Histochemistry 1991;96:169), monocytes and macrophages, placenta cytotrophoblast and Hofbauer cells (Acta Histochem 2003;105:253), fibroblasts
Positive staining (disease): osteoclast disorders including osteoclast-like giant cell neoplasms (Mod Path 2006;19:161) and inflamed synovium (Ann Rheum Dis 1993;52:182)
Negative staining: cartilage (Ann Rheum Dis 2000;59:448)
References: OMIM 193210
Also called Campath-1 and epididymal secretory protein E5
CD52 antibodies are lytic for target cells, both with human complement and via antibody dependent cellular cytotoxicity
Uses: antibodies (Alemtuzumab) are used for long-term depletion of T lymphocytes from donor marrow to prevent graft versus host disease (Bone Marrow Transplant 2000;26:69, Transplantation 1999;67:620); also to treat refractory CLL; high serum levels are poor prognostic marker in CLL (Cancer 2004;101:999); may treat other malignancies (see CD52+ disorders below), including pure red blood cell aplasia (Br J Haematol 2003;123:278); differentiates eosinophils (CD52++) from neutrophils (CD52 weak/negative)
Micro images: figures 1A/B: normal tonsil shows lymphocytic staining, but there is no staining of connective tissue or vessels; C: follicular lymphoma is CD52+; D: Reed-Sternberg cells (arrows) are CD52-; figures 2A/B: SLL/CLL is CD52+; C: anaplastic lymphoma is CD52+; D: adult T cell leukemia/lymphoma is CD52+
Positive staining (normal): thymocytes, lymphocytes, monocytes/macrophages, eosinophils, mast cells (Clin Lymphoma Myeloma 2006;6:478), epithelial cells lining the male reproductive tract
Positive staining (disease): most lymphoid malignancies (variable levels, J Clin Path 1994;47:313), including lymphoplasmacytic lymphoma (100%, AJCP 2005;124:414), myeloma (5-10%, AJCP 2004;121:482), hairy cell leukemia (Am J Hematol 2003;74:227); T cell large granular lymphocytic leukemia (Leuk Lymphoma 2005;46:723), Langerhans cell histiocytosis (Pediatr Blood Cancer 2005;44:251)
Negative staining: neutrophils, Langerhans cells (normal), lymphocytes in paroxysmal nocturnal hemaglobinuria, Reed-Sternberg cells in Hodgkin’s lymphoma
References: OMIM 114280
Most specific and reliable pan-leukocyte marker
Encodes member of tetraspanin family, a cell surface protein with 4 hydrophobic domains that mediate signal transduction
Also has adhesion/activation functions
Upregulated in macrophages exposed to lipopolysaccharide (Mol Cells 2004;17:125)
May transduce CD2-generated signals in T cells and natural killer cells
May be a thymocyte selection marker, with CD69 (Int Immunol 2002;14:249)
Familial deficiency is associated with recurrent infectious diseases (Clin Diagn Lab Immunol 1997;4:229)
Uses: no significant clinical use by pathologists
Positive staining (normal): leukocytes; also dendritic cells, osteoclasts and osteoblasts, mesangial cells (Kidney Int 2003;63:534)
Positive staining (disease): radioresistant tumor cells
Negative staining: platelets, red blood cells, non-hematopoietic cells
References: OMIM 151525
Also called ICAM-1 (intercellular adhesion molecule 1)
Ligand for LFA-1 (CD50)
Receptor for rhinovirus (Proc Natl Acad Sci USA 1991;88:7993), malaria infected erythrocytes (Infect Immun 2006;74:3262, Proc Natl Acad Sci USA 2000;97:1766)
Involved in adhesion of neutrophils to endothelium at site of inflammation
Reacts with CD11a / CD18 or CD11b / CD18 resulting in immune reaction or inflammation
Reduced expression in endometrial cells may contribute to endometriosis (Immunol Lett 2002;80:49)
Uses: CD54 negative gastric carcinoma cells may predict nodal metastases (Dig Dis Sci 2005;50:2224); low CD54 levels associated with poor prognosis in childhood ALL (Br J Biomed Sci 2003;60:149)
Micro images (Mod Path subscribers): keratoacanthoma; poorly differentiated squamous cell carcinoma
Positive staining (normal): broad, B and T cells and B cell precursors, monocytes, osteoclasts, endothelial cells, epithelial cells (various)
Positive staining (tumors): keratoacanthoma (more in fully developed lesions with inflammatory infiltrate), cutaneous squamous cell carcinoma (focal if well differentiated, intense if poorly differentiated, Mod Path 2003;16:8)
Negative staining (tumors): intravascular B cell lymphoma
References: OMIM 147840
Also called complement decay accelerating factor (DAF)
Gene encodes Cromer blood group (Blood Group Antigen Gene Mutation Database)
Binds C3bBb (alternative pathway convertase) and C4b2a (classical pathway convertase) to accelerate decay of the C3 convertases; protects against inappropriate complement activation (J Biol Chem 2005;280:2569)
Receptor for CD97, echovirus (Proc Natl Acad Sci USA 2002;99:10325) and Coxsackie B virus (J Virol 1998;72:9407)
Also is part of lipopolysaccharide-induced receptor complex (Eur J Immunol 2003;33:1399)
Genetic defects that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria (PNH); also cause defective platelets, granulocytes, erythrocytes and possibly lymphocytes
CD55 deficiency is common in patients treated with Campath (anti-CD52), which may predispose to PNH (Transplant Proc 2006;38:1750)
A minor population of CD55-CD59 negative granulocytes and red blood cells predicts a good response to immunosuppressive therapy in patients with acquired aplastic anemia (Blood 2006;107:1308)
Loss of CD55 is associated with poor prognosis in breast cancer (Clin Cancer Res 2004;10:2797); however high expression is associated with poor prognosis in colorectal carcinoma (Cancer Immunol Immunother 2003;52:638)
Case reports: pregnant woman with thrombocytopenia due to PNH
Uses: diagnosis of PNH (AJCP 2006;126:781)
Micro images: breast carcinoma staining #1; #2; #3
Positive staining (normal): all hematopoietic cells and all cell types in intimate contact with complement proteins; also epithelial cells lining extracellular compartments, body fluids, extracellular matrix
References: OMIM 125240
Also called Leu7, beta-1,3-glucuronyltransferase 1, glucuronosyltransferase P
Glycoprotein with cell adhesion functions
May define a phenotype associated with replicative senescence in HIV specific CD8+ T cells (Blood 2003;101:2711)
Case reports: 6 year old girl with B-ALL and CD56 and CD57 coexpression (Pediatr Hematol Oncol 2004;21:677)
Uses: marker of NK cells and neuroendocrine tumors, helps distinguish high grade prostatic adenocarcinoma (CD57+) from high grade urothelial carcinoma (CD57-)
Micro images: metanephric adenoma (figure E); large granular lymphocytic leukemia
Positive staining (normal): NK subset, T cell subset, neuroectodermal tissue, retina, brain, prostate, renal proximal tubules
Positive staining (disease): leukemia/lymphomas - autoimmune lymphoproliferative syndrome, hepatosplenic T cell lymphoma (some), nodular lymphocyte predominant Hodgkin lymphoma (CD57+ rosettes in 50%, AJCP 2003;119:192), pre T-ALL (occasional), T-cell large granular lymphocytic leukemia (some)
nerve sheath origin lesions - benign epithelioid nerve sheath tumor (AJSP 2005;29:39), chordoma, dendritic cell neurofibroma with pseudorosettes (AJSP 2001;25:587), melanotic neuroectodermal tumor of infancy, MPNST (expression decreases with tumor grade, AJSP 2003;27:1337), nerve sheath myxoma (AJSP 2005;29:1615),
Positive staining (tumors): other - carcinoid tumors, desmoplastic nested spindle cell tumor of liver (AJSP 2005;29:1), desmoplastic small round cell tumor (AJSP 1998;22:1314), germ cell tumor (embryonal carcinoma, seminoma), mesenchymal chondrosarcoma, metanephric adenoma (AJSP 2001;25:1290), neuroendocrine carcinoma of prostate (AJSP 2006;30:684) and other sites, PNET, prostatic adenocarcinoma, renal carcinoid, renal clear cell carcinoma (some), small cell carcinoma of lung and other sites, spindle cell thymoma (AJSP 2001;25:111), synovial sarcoma, thyroid papillary carcinoma (Cancer 2006;108:331)
Negative staining: B cells, monocytes, red blood cells, platelets; NK/T cell lymphoma-nasal type, Wilm’s tumor
References: OMIM 151290
Also called LFA-3 (lymphocyte function associated antigen)
Ligand for CD2 (J Mol Biol 2001;312:711)
Mediates adhesion between NK cells and target cells (J Immunol 2003;170:294), antigen presenting cells and T cells (Cell 1999;97:791), thymocytes and thymic epithelial cells
High serum levels in Hepatitis B, associated with liver cell damage (World J Gastroenterol 2006;12:4237)
Uses: detect minimal residual disease in pre-B ALL (Haematologica 2003;88:1245)
Micro images: various images; lymphoma (type unknown)
Positive staining (normal): leukocytes (but not mature B cells), pre B cells, erythrocytes, endothelial cells, epithelial cells, fibroblasts, cardiac muscle (J Clin Path 1990;43:893)
Positive staining (disease): pre-B ALL (AJCP 2005;123:119)
Negative staining: mature B cells
References: OMIM 153420
Also called protectin, complement regulatory molecule
Regulates complement mediated cell lysis by inhibiting formation of membrane attack complex (MAC); binds to C8 or C9 components, preventing incorporation of multiple copies of C9 required for complete formation of osmolytic core
Also makes cells susceptible to NK cell mediated cytotoxicity (J Immunol 2006;176:2915)
Genetic defects that reduce both CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria (PNH); also cause defective platelets, granulocytes, erythrocytes and possibly lymphocytes
Low CD59 levels may also cause PNH-like symptoms after Campath therapy (Transplant Proc 2006;38:1750)
Not a particularly good marker for detecting PNH+ monocytes (AJCP 2006;126:781)
In diabetes, glycation may inhibit CD59, causing MAC deposition in vessels, leading to vascular complications (Diabetes 2004;53:2653)
Naegleria (Infect Immun 2006;74:1189), Borrelia (J Immunol 2003;170:3214) and HIV (J Gen Virol 1997;78:1907) may resist complement mediated lysis via a surface CD59 like protein
Uses: no significant clinical use by pathologists
Positive staining (normal): most cells
Positive staining (disease): squamous cell carcinoma of head and neck (J Oral Path Med 2006;35:560)
References: OMIM 107271
Use of CD60, CDw60 and CD60a, CD60b and CD60c is inconsistent
Not proteins, but oligosaccharides present on gangliosides
CD60a: GD3 - carbohydrate structure
CD60b: 9-O-acetyl-GD3 - carbohydrate structure
CD60c: 7-O-acetyl-GD3 - carbohydrate structure
Antibodies provide costimulatory signals for T cells
Expressed on most T cells in autoimmune lesions (Immunol Invest 2001;30:67)
CD8+ CD60+ T cells may regulate IgE memory responses and isotype switching (Hum Immunol 2005;66:1029)
Associated with Th1 immune response in skin (Br J Dermatol 2003;149:739)
Uses: no significant clinical use by pathologists
Positive staining (normal): platelets, T cells (30%, Carbohydr Res 2000;329:791), thymic epithelium, activated keratinocytes, melanocytes, synovial fibroblasts, glomeruli, smooth muscle cells, astrocytes; also epithelium of reproductive system, exocrine and endocrine glands (Histochem J 2000;32:447)
Positive staining (disease): T cells in rheumatoid arthritis and psoriasis, monocytes in cutaneous T cell lymphoma (Acta Derm Venereol 2001;81:263)
Negative staining: B cells, granulocytes, monocytes
References: glycolipids
CD60a
Not a protein: oligosaccharide present on gangliosides
GD3 - carbohydrate structure
Uses: no significant clinical use by pathologists
CD60b
Not a protein: oligosaccharide present on gangliosides
9-O-acetyl-GD3 - carbohydrate structure
May protect tumor cells from apoptosis (Int J Cancer 2006;119:67)
Uses: no significant clinical use by pathologists
Positive staining (disease): Leishmania promastigotes (Glycobiology 2003;13:351)
CD60c
Not a protein: oligosaccharide present on gangliosides
7-O-acetyl-GD3 - carbohydrate structure
Uses: no significant clinical use by pathologists
Also called integrin beta 3 chain
Combines with CD41 (integrin alpha IIb) to form platelet glycoprotein IIb/IIIa, a receptor for fibrinogen, fibronectin, plasminogen, prothrombin, thrombospondin, vitronectin and von Willebrand factor
Combines with CD51 to form receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor
CD51-CD61 is present on endothelium, endothelial cells, smooth muscle, some B cells, monocytes, macrophages, platelets, osteoclasts, mast cells, fibroblasts and tumor cells
Platelet activation causes a conformation change in GPIIb/IIIa, enabling the binding of soluble fibrinogen and forming a platelet plug
CD61 defects cause Glanzmann thrombasthenia, an autosomal recessive disorder and the most common inherited platelet disease
CD61 has role in pathogenesis of asthma (Am J Respir Crit Care Med 2005;172:67)
Polymorphisms may cause premature coronary artery disease (Archives 1999;123:1223)
High pre-kidney transplant levels associated with acute rejection (Transplant Proc 2003;35:1360)
Uses: identify platelets, megakaryocytes, platelet thrombi; distinguish TTP (diffuse CD61+ platelet rich thrombi) from DIC (no/sparse thrombi, Cardiovasc Path 2005;14:150); count platelets in thrombocytopenic patients (Br J Haematol 2001;112:584)
Micro images: AML-M7 #1; #2; #3; #4; #5 (figures C, D); dysplastic megakaryocytes #1; #2
Positive staining (normal): platelets, megakaryocytes, myeloid progenitor cells, endothelial cells
Positive staining (disease): AML M7, AML M6 (some), blasts in transient myeloproliferative disorder (AJCP 2001;116:204)
Negative staining: AML M0-M5, M6 (most)
References: J Clin Invest 2005;115:3363 (review), OMIM 173470
Also called E selectin, endothelial (leukocyte) adhesion molecule-1, ELAM1, SELE
Ligand for sialyl-Lewis X (CD15s); also CD43 (Blood 2006;107:1421), CD44 (J Exp Med 2005;201:1183), CD162/PSGL-1 (Am J Physiol Cell Physiol 2005;289:C415) and tumor cells (Cancer Res 2005;65:5750)
Inhibited by hCG (Anticancer Res 2005;25:1811)
Mediates leukocyte rolling (causes slow rolling, which may assist with adhesion) and adhesion to activated endothelium at inflammatory sites
Also associated with atherosclerosis, tumor cell adhesion during hematogenous metastasis (Cancer Res 2006;66:9117)
Patients with Leukocyte Adhesion Deficiency 2 syndrome (OMIM 266265), who lack sialyl Lewis X component of selectin counter-receptors, suffer recurrent pyogenic infections
Homozygosity for Ser128Arg polymorphism associated with recurrent venous thromboembolism (Arch Intern Med 2006;166:1655) and myocardial infarction (Arterioscler Thromb Vasc Biol 2003;23:783), due to increased rolling and adhesion of neutrophils and mononuclear cells, or alteration of lymphocytes binding to E selectin (J Immunol 2002;169:5860)
Other mutations also associated with vascular disease (Brain Res 2006;1108:221)
High serum levels associated with insulin resistance in type 2 diabetes (Metabolism 2005;54:376), vascular disease in type 1 diabetes (J Diabetes Complications 2006;20:188), relapse in AML (Hematology 2002;7:83)
Cryptococcus induces WBC surface L-selectin shedding to reduce WBC infiltration into infected tissues (J Infect Dis 2005;191:1361)
Trypanosoma cruzi produces a mucin that, through CD62L binding, inhibits T cell proliferation (Int Immunol 2004;16:1365)
Uses: no significant clinical use by pathologists
Micro images: normal tonsil vessels; normal brain and renal carcinoma; experimental acute pancreatitis
Positive staining (normal): endothelium after cytokine stimulation
Positive staining (disease): endothelium in chronic inflammatory disorders of skin and synovium, hemangiomas (Am J Path 1996;148:1181)
References: OMIM 131210
Also called L selectin, LECAM-1, SELL
Mediates lymphocyte homing to high endothelial venules of peripheral lymphoid tissue, migration of lymphocytes to inflamed tissue via leukocyte rolling on activated endothelium
Binds to CD34 (Adv Exp Med Biol 1998;435:55)
High serum levels associated with diabetic retinopathy (Ocul Immunol Inflamm 2003;11:123), relapse in AML (Hematology 2002;7:83)
Reduced levels on T cells in neonatal pertussis (AJCP 2000;114:35)
Loss of expression is associated with progression of low grade MALT (Mod Path 2001;14:798)
Functionally active endothelial L-selectin ligands cause lymphocyte infiltration into transplanted hearts at the onset and during acute rejection episodes (Am J Path 1999;155:1303)
Uses: may distinguish lymphomatoid hypersensitivity reactions from true endogenous T-cell dyscrasia (J Cutan Pathol 2005;32:12)
Micro images: rat thymus
Positive staining (normal): B, T, NK cells (some), monocytes, neutrophils, eosinophils, trophoblast (Science 2003;299:405), epidermal Langerhans cells
References: OMIM 153240, Am J Path 1999;155:1013, J Cell Mol Med 2005;9:255
Also called P selectin, PADGEM, SELP
Interaction with CD162 mediates tethering and rolling of leukocytes on the surface of activated endothelial cells
Also (a) mediates delivery of lymphocytes to high endothelial venules (with CD62L); (b) a platelet alpha-granule membrane protein that redistributes to the plasma membrane during platelet activation and degranulation; (c) has procoagulant activity (Trends Mol Med 2004;10:179)
Constitutive expression in inflammation may contribute to tissue destruction, atherogenesis and thrombosis
Reduced expression in gray platelet syndrome (139090), advanced melanoma (Am J Path 1998;152:679)
Increased expression in Takayasu's arteritis (Circ J 2006;70:600)
Increased serum levels associated with atherosclerosis (Eur Heart J 2003;24:2166)
Val640Leu polymorphism is associated with thromboembolic stroke (Hum Mol Genet 2004;13:389)
Endothelial P-selectin has important role in pathogenesis of cerebral malaria (Am J Path 2004;164:781)
Promotes metastases by tumor cell binding (Glycobiology 2007;17:185)
Uses: distinguishing heparin-induced thrombocytopenia without and with thrombosis (Thromb Haemost 1999;82:1255)
Micro images: megakaryocytes in bone marrow #1; #2; #3; endothelial cell staining in tonsillar tissue; expression in mice infected with Plasmodium berghei; expression in rats with lung injury
Positive staining (normal): platelets, megakaryocytes, activated endothelial cells (membranes of Weibel-Palade bodies)
Negative staining: sinusoidal endothelium (Am J Path 1993;142:481)
References: OMIM 173610
Also called NKI-C3 (J Natl Cancer Inst 1992;84:422), lysosomal membrane-associated glycoprotein 3, LAMP-3, melanoma associated antigen, ME491
Member of tetraspanin superfamily of integral membrane proteins - tetraspanins form lateral associations with integrins and may act as organizers of multimolecular networks that modulate integrin mediated signaling, cell morphology, motility and migration
Intracellular lysosomal / endosomal / granule protein, in Weibel-Palade bodies of endothelium and in azurophil granules of neutrophils (Am J Pathol 1994;144:1369)
Serves as adaptor protein that links its interaction partners to the cell’s endocytic machinery (Proc Natl Acad Sci USA 2003;100:15560)
Marker of platelet activation that is transported to surface after activation; also modulates platelet spreading on immobilized fibrinogen (Thromb Haemost 2005;93:311)
Associated with early stages of melanoma progression (Cancer Res 1988;48:2955)
Deficiency associated with Hermansky-Pudlak syndrome (OMIM 203300)
High pre-kidney transplant levels are associated with acute rejection (Transplant Proc 2003;35:1360)
Used for basophil activation tests (Allergy 2006;61:1084)
CD63 pathway from host multivesicular bodies provides essential lipids to Chlamydia to maintain productive intracellular infection (J Cell Sci 2006;119:350)
Uses: marker of melanoma (although non-specific) and melanocytic tumors; may be useful for other tumors (see below)
Micro images: cellular neurothekeoma; Chlamydia inclusions #1; #2; #3
Positive staining (normal): activated platelets, endothelium, fibroblasts, macrophages, mast cells, osteoclasts; weakly expressed on B and T cells and granulocytes; also bronchial glands, neural tissue (brain white matter and peripheral nerves), nevi, salivary glands, smooth muscle, synovial lining cells
Positive staining (tumors): angiomyolipoma (100%, Archives 2001;125:751), atypical fibroxanthoma (33%), breast carcinoma (100%, Am J Pathol 1998;153:973), carcinoids (some), cellular fibrous histiocytoma (50%), cellular neurothekeoma (81%, Mod Path 2004;17:230), clear cell fibrous papule of nose (83%, Am J Dermatopathol 2005;27:296), deciduoid mesothelioma (67%, AJSP 2000;24:285), dermatofibrosarcoma protuberans (90%, AJCP 1992;97:478), histiocytic sarcoma, juvenile xanthogranuloma (60%), melanoma (90%), primitive nonneural granular cell tumors of skin (90%, AJSP 2005;29:927), renal oncocytoma (apical and polar staining) and renal chromophobe carcinoma-eosinophilic variant (diffuse staining, Virchows Arch 2005;447:938), reticulohistiocytoma (50%), thyroid medullary carcinoma (some), xanthoma (80%)
Negative staining: epithelioid cell histiocytoma, Langerhans cell histiocytosis
References: OMIM 155740, AJCP 2006;126:554
Also called Fc gamma RI
High affinity receptor binds to Fc region of IgG
Important in phagocytosis via receptor-mediated endocytosis of IgG-antigen complexes
Mediates antigen capture for presentation to T cells, antibody-dependent cellular cytotoxicity, release of cytokines and reactive oxygen intermediates
Also binds to C reaction protein and mediates its effects (J Biol Chem 2005;280:25095)
Denge fever immune complexes enter macrophages via CD64 (J Virol 2006;80:10128)
Uses: high neutrophil CD64 levels predict sepsis (Archives 2006;130:654, Lab Hematol 2005;11:137), early onset of infection in neonates (Pediatr Res 2004;56:796), infection in rheumatoid arthritis patients (J Rheumatol 2006;33:2416)
Positive staining (normal): antigen presenting cells including macrophages/monocytes, activated granulocytes, dendritic cells; also early myeloid cells
Positive staining (disease): AML M3 (usually); M4, M5 (AJCP 1998;110:797), M0-M2 (variable);
Negative staining: AML M7
Flow cytometry images: levels in patient with elevated neutrophil CD64
References: OMIM 146760
Also called VIM2, ceramide-dodecasaccharide, dimeric sialyl-CD15
Adhesive carbohydrate (not a protein) that appears to be significant risk factor for extravascular AML infiltration (Leuk Res 2001;25:847)
Uses: myeloid antigen used in flow cytometry
Positive staining (normal): myeloid cells, monocytes
Negative staining: lymphocytes
Positive staining (disease): AML
CD65s
Also called sialylated-CD65
A carbohydrate antigen, not a protein
Appears when CD34 antigen disappears
Antibodies may either recognize CD65s (sialylated) or CD65 (non-sialylated)
Uses: for acute leukemia cell typing and to identify a subset of pre-pre-B ALL (AJCP 2002;117:380)
Positive staining (normal): granulocytes, monocytes
Positive staining (disease): myeloid leukemia, low levels in AML M0-M1 (Leukemia 2003;17:1544)
Also called CEACAM1, biliary glycoprotein, BGP, C-CAM
Primordial protein of carcinoembryonic antigen (CEA) family
Cell adhesion molecule capable of activating neutrophils
Receptor for Neisseria gonorrhoeae and N. meningitides; binding prevents epithelial detachment, a defense mechanism that hinders colonization (J Cell Biol 2005;170:825); CD66a+ B cells are also killed by N. gonorrhoeae (Infect Immun 2005;73:4171)
With osteopontin, may mediate invasion of extravillous trophoblast at maternal-fetal interface (J Clin Endocrinol Metab 2005;90:5407)
Interactions with CEA inhibit NK cell cytotoxicity (J Immunol 2005;174:6692)
Downregulated in breast (J Histochem Cytochem 1997;45:957), colorectal, endometrial, hepatocellular, prostate (particularly Gleason grade 4/5, Hum Path 2002;33:290) and renal cell carcinoma (J Pathol 2004;204:258)
Uses: expression predicts metastases in cutaneous melanoma (J Clin Oncol 2002;20:2530)
Micro images: cutaneous melanoma; metastatic melanoma; expression at maternal-fetal surface; various breast lesions; colon; rectum
Positive staining (normal): granulocytes, lymphocytes, epithelial cells, endothelial cells, prostate glands and ducts (dense), bile canaliculi between liver cells, extravillous trophoblast (Am J Pathol 2000;156:1165)
Positive staining (disease): low grade prostate carcinoma
Negative staining: high grade (Gleason 4/5) prostate carcinoma
References: OMIM 109770
CD66b
Also called CEACAM8. NCA-95, CGM6; formerly CD67
Cell adhesion molecule capable of activating neutrophils
Increased expression on peripheral blood neutrophils and eosinophils of rheumatoid arthritis patients (Scand J Immunol 1999;50:433)
Uses: marker for granulocytes
Micro images: neutrophils adhering to infracted cardiomyocytes
Positive staining (normal): granulocytes
Positive staining (disease): chronic myelogenous leukemia (Cancer Res 1990;50:6534), cardiomyocytes in areas of infarction (Cardiovasc Res 1999;41:603)
CD66c
Also called nonspecific cross reactive antigen, CEACAM6, NCA 50/90
Cell adhesion molecule capable of activating neutrophils
Uses: no significant clinical use by pathologists
Positive staining (normal): granulocytes
Positive staining (disease): ALL (43%, BMC Cancer 2005;5:38)
References: OMIM 163980
CD66d
Also called CEACAM3, CGM1
Cell adhesion molecule capable of activating neutrophils
Has important role in control of pathogens by the innate (opsonin-independent) immune system (J Exp Med 2004;199:35)
Used by Neisseria. gonorrhoeae, Moraxella catarrhalis, and Hemophilus influenzae to anchor themselves to and invade host cells
N. gonorrheae has an opacity-associated (Opa) protein that binds to CEACAM3 (J Biol Chem 2001;276:17413)
Uses: no significant clinical use by pathologists
Positive staining (normal): granulocytes
References: OMIM 609142
Also called CEA, carcinoembryonic antigen, CEACAM5
Either polyclonal (pCEA) or monoclonal (mCEA)
Normally detected in glycocalyx of fetal epithelial cells
May play a role in the metastasis of cancer cells
Usually considered an epithelial marker with strong staining in adenocarcinomas
Case reports: CEA immunostaining in benign multicystic mesothelioma of the peritoneum (not typical, Archives 2001;125:944)
Uses:
Colorectal carcinoma: monitor serum levels (elevated in 72-97%) to detect recurrence (World J Gastroenterol 2006;12:3891), elevated preoperative serum levels are poor prognostic factor (Int J Cancer 2002;101:545); caution - elevated levels also present in cirrhosis, biliary obstruction, hepatitis, inflammatory bowel disease, smokers, post-surgical bowel sequestration with mucocele (Archives 2003;127:1376)
Adenocarcinoma (lung) vs. epithelioid mesothelioma: monoclonal CEA is 97% specific for lung adenocarcinoma (Histopathology 2006;48:223); exhibits diffuse cytoplasmic staining with membrane enhancement in adenocarcinoma, negative in mesothelioma
Adenocarcinoma (lung) vs. reactive mesothelial cells in fluid cytology: positive staining is 76% sensitive (AJCP 2001;116:709)
Breast cancer vs. benign breast disease in FNA fluid: high levels are suggestive of malignancy (Archives 2004;128:1251)
Cysts (various): CEA levels over 5 ng/dl in ascites fluid are associated with malignancy (J Clin Pathol 2001;54:831); but fluid in cysts may be CEA+ even when benign (Mod Path 1998;11:1171)
Hepatocellular carcinoma: canalicular pattern for polyclonal CEA has 50-90% sensitive for hepatocellular carcinoma, >95% specific (Mod Path 2002;15:1279); CEA-Gold is 76% sensitive (AJSP 2002;26:978); monoclonal CEA is usually negative (Hum Path 2002;33:1175)
Microvillous inclusion disease of small intestine: cytoplasmic staining of surface enterocytes (AJSP 2002;26:902)
Pancreatic adenocarcinoma: monoclonal CEA is 92% sensitive for metastases vs. 0% for bile duct adenoma (AJSP 2005;29:381)
Micro images: ampulla of Vater-Paneth cell carcinoma (figure G); breast adenoid cystic carcinoma; cervical adenocarcinoma-signet ring cell type (figure D); cervical adenocarcinoma-intestinal differentiation (figure D); cervical adenoid cystic carcinoma #1; #2; colon carcinoma #1; #2; colon inverted hyperplastic polyp (normal colon at upper right is CEA neg); gastric adenocarcinoma metastatic to colon; hepatocellular carcinoma (polyclonal CEA); hepatocellular carcinoma vs. cholangiocarcinoma (note different staining patterns); hepatocellular carcinoma-clear cell variant (figure A); liver-poorly differentiated adenocarcinoma (figure 4D); lung adenocarcinoma metastatic to ovary (figure 2B); medullary thyroid carcinoma; Paget’s disease of vulva; Paget’s disease of scrotum; peritoneal benign multicystic mesothelioma (an atypical finding, figure 2F); secretory meningioma #1; #2; sweat gland carcinoma #1 (figure 8B); various images-quality control
Cytology images: adenocarcinoma in pleural fluid; cholangiocarcinoma
Positive staining (normal): granulocytes and epithelial cells (apical surfaces); also biliary tract including gallbladder, colon (fetal), hepatocytes, prostatic secretory cells (25%), small intestinal crypts; small intestinal goblet cell mucin (not intracytoplasmic), thyroid cell nests and C cells
Positive staining (tumors): bile duct tumors (benign or malignant), bladder adenocarcinoma and benign tumors, breast ductal and secretory carcinoma, CASTLE (AJSP 2006;30:994), cervical adenocarcinoma (Archives 2003;127:1586) and squamous cell carcinoma, cholangiocarcinoma (monoclonal and polyclonal, cytoplasmic and luminal but not canalicular pattern), chordoma (variable), choriocarcinoma of placenta and testes (25%, AJCP 1986;86:538), clear cell papulosis of skin, colorectal carcinoma (almost all, throughout cell surface), endometrial adenocarcinoma (50%, focal, AJSP 1982;6:151 but negative with monoclonal CEA, Mod Path 2006;19:1091), gallbladder dysplasia/carcinoma (cytoplasmic and luminal staining), gastric adenocarcinoma, hepatoblastoma (polyclonal antibody, canalicular pattern, particularly in fetal subtype), hepatocellular carcinoma (polyclonal CEA, canalicular pattern, 90%, Hum Path 2005;36:1226), hepatoid adenocarcinoma (AJSP 2003;27:1302), lung adenocarcinoma, lung squamous cell carcinoma (nonkeratinizing, 77%, Mod Path 2006;19:417), neuroendocrine (including carcinoid) tumors (variable), ovarian mucinous tumors including carcinoma (92%, AJCP 2001;116:246), Paget’s disease (breast, vulva, scrotum), pancreatic adenocarcinoma (including foamy gland variant, AJSP 2000;24:493 and lining of cysts, Mod Path 2005;18:1157), penile clear cell carcinoma (AJSP 2004;28:1513), salivary gland tumors (various), secretory meningioma; sweat gland tumors including carcinoma (73%, Archives 2001;125:498), synovial sarcoma (variable), thymoma, thyroid medullary carcinoma, urothelial carcinoma
Negative staining: breast carcinoma (usually), endometriosis, mesothelioma (including testis, AJSP 2006;30:1), ovarian endometrioid and serous carcinoma (Archives 1999;123:909), prostate adenocarcinoma (AJCP 2002;117:471), renal cell carcinoma, thymic carcinoma (usually), thyroid carcinoma other than medullary
CD66f
Also called pregnancy-specific beta-1 glycoprotein, PSG1
May be involved in immune regulation, protection of fetus from maternal immune system
Released into maternal circulation during pregnancy
Low levels in maternal blood predict spontaneous abortion
Uses: no significant clinical use by pathologists
Micro images: various images (pages 20-22)
Positive staining (normal): syncytiotrophoblasts, fetal liver, myeloid cells
Positive staining (disease): hydatidiform and invasive moles, choriocarcinoma (J Clin Pathol 1977;30:19)
References: OMIM 176390
Deleted; now CD66b
Also called KP1, macrosialin
May have role in macrophage phagocytic activities
Specific to lysosomes, not cell lineage; epithelial cells activated by E coli may be CD68+ (Toxicol In Vitro 2002;16:405)
Binds to tissue and organ specific lectins or selectins, allowing homing of macrophage subsets to particular sites
Uses: marker of histiocytes and histiocytic tumors; presence in postportoenterostomy liver biopsies for extrahepatic biliary atresia is associated with favorable prognosis (J Pediatr Surg 2005;40:1252)
Micro images: acute demyelinating disease; AML-M4; AML-M5; atypical epithelioid angiomyolipoma of kidney; breast carcinoma-treatment effect (figure C); cholesterol granuloma of temporal bone; Castleman’s disease; chronic myelomonocytic leukemia with eosinophilia (figure C); Crohn’s disease; crystal storing histiocytosis within lymphoma; endometrial nodular histiocytic hyperplasia (figure 3); Erdheim-Chester disease #1-lung (figure 5); #2-liver (figure 5); follicular dendritic cell tumor; gastrointestinal stromal tumor with osteoclast-like giant cells (figure 3b); Gaucher’s disease (presumptive) in spleen; giant cell granuloma of temporal bone (figure C); granular cell tumor (figure 2B); histiocytic sarcoma (figure 5); HIV associated encephalopathy; inflammatory demyelinating pseudotumor (brain); juvenile xanthogranuloma-adult (figure 4); Kikuchi’s disease; Kikuchi-like lymphadenopathy #1 in lupus; #2; #3; Kupffer cells in alcoholic liver disease (figure 6); Langerhans cell histiocytosis; leiomyosarcoma with osteoclast-like giant cells (figure D); lymph node-tingible body macrophages; multiple sclerosis; myeloid sarcoma #1 (figure 1d); #2-spine; #3-uterus; nerve-Wallerian degeneration; plexiform fibrohistiocytic tumor #1 (figure 3); plasmacytoid monocyte tumor; Rosai-Dorfman disease #1-figure D; splenic hamartoma (figure 3B); thyroid gland giant cell granuloma (figure C); viral myocarditis; xanthogranulomatous pyelonephritis (figure 4); quality control
Micro images (Mod Path subscribers): Kupffer cells in normal liver; Kupffer cells in severe non-alcoholic steatohepatitis (figure B)
Positive staining (normal): macrophage/monocytes (including Kupffer cells and microglia), basophils, dendritic cells, fibroblasts (Verh Dtsch Ges Pathol 2003;87:215, Ann Rheum Dis 2004;63:774), Langerhans cells, mast cells, myeloid cells, CD34+ progenitor cells, neutrophils, osteoclasts, activated platelets, B and T cells; fetal small intestinal inclusions (Cesk Patol 2001;37:7)
Positive staining (tumors): AML-M4/M5, angiosarcoma, atypical fibroxanthoma, B cell lymphoma (some), blastic NK lymphoma, calcifying aponeurotic fibroma (Hum Path 1998;29:1504), cellular fibrous histiocytoma (83%, J Cutan Pathol 2006;33:353), chronic intervillositis (Hum Path 2000;31:1389), dermal dendrocytoma, dermatofibroma (42%, J Cutan Pathol 2006;33:353), Erdheim-Chester disease (AJSP 1999;23:17), follicular dendritic cell tumor (AJSP 1998;22:1048), Gaucher cells (AJCP 2004;122:359), giant cell angioblastoma, giant cell tumors (extrahepatic biliary tree- AJSP 2006;30:495; soft tissue-AJSP 2000;24:386, synovial type-Hum Path 2003;34:670), granular cell astrocytoma (AJCP 2006;126:602), granular cell tumor (Archives 2004;128:771), granulocytic (myeloid) sarcoma (AJSP 1997;21:1156), hairy cell leukemia, hereditary disorders (ceruloplasmin deficiency-macrophages in striatum #1; #2), histiocytic sarcoma (AJSP 2001;25:1372), HIV encephalopathy (Am J Pathol 2004;164:2089), inflammatory myofibroblastic tumor/pseudotumor (AJCP 2003;120:56), interdigitating dendritic cell sarcoma (AJSP 2002;26:530, AJCP 2001;115:589), juvenile xanthogranuloma (AJSP 2003;27:579), Kikuchi’s disease (AJSP 1999;23:1040), Langerhans cell histiocytosis (usually, Blood 2001;97:1241), malignant fibrous histiocytoma, mastocytosis and mast cell disease (AJSP 2000;24:703), melanoma (Mod Path 1999;12:1072), mycobacterial pseudotumor (AJSP 1999;23:656), myelodysplasia bone marrow nodules (AJCP 2003;120:874), neuroma, nodular fasciitis, osteoclast-like giant cells in tumors of pancreas and urinary tract (Archives 1998;122:266, Mod Path 2006;19:161), pigmented villonodular synovitis (Hum Path 2003;34:65), pleomorphic xanthoastrocytoma, plexiform xanthomatous tumor (AJSP 2002;26:1302), primitive non-neural granular cell tumor of skin (AJSP 2005;29:927), renal cell carcinoma (AJCP 1995;103:425), reticulohistiocytoma (AJSP 2006;30:521), Rosai-Dorfman disease (Mod Path 2001;14:172), schwannoma, signet ring-like cells (benign, AJCP 2001;115:249), splenic diffuse hemangioma (AJSP 1997;21:827), splenic littoral cell angioma (AJSP 2006;30:1036), steatohepatitis (Mod Path 2002;15:699), Whipple’s disease, xanthelasma (Archives 2003;127:e417), xanthogranulomatous pyelonephritis (Archives 2005;129:e209), xanthoma (Hum Path 2003;34:814)
Negative staining: atypical fibrous histiocytoma (AJSP 2002;26:35), megakaryocytes
References: OMIM 153634, AJCP 2004;122:794 (comparison with CD163)
Also called activation inducer molecule (AIM), early activation antigen (EA-1)
Earliest inducible cell surface glycoprotein acquired during lymphoid activation
Involved in early events of T cell, NK cell, monocyte and platelet activation
Associated with Th-1 T cell differentiation and associated cytokines (IL-2, TNF-alpha, interferon-gamma, Hum Path 2002;33:330)
Highly expressed on T cells from inflammatory infiltrates of rheumatoid arthritis (Clin Exp Rheumatol 2004;22:331), viral hepatitis, autoimmune thyroid disorders
Expression on CD3+ and CD8+ peripheral blood T cells correlates with acute graft rejection in renal allograft recipients (Transplantation 2003;76:190)
May promote lymphocyte retention in lymphoid organs (Nature 2006;440:540)
Uses: no significant clinical use by pathologists
Positive staining (normal): activated T cells, B cells, NK cells, neutrophils, eosinophils, epidermal Langerhans cells, platelets, thymocytes
Positive staining (disease): peripheral T cell lymphoma (AJCP 2003;120:866)
References: OMIM 107273
Also called CD27 ligand
Cytokine that belongs to tumor necrosis factor ligand family
Has role in T cell activation (J Immunol 2006;176:7726)
Induces T cell proliferation and enhances generation of cytolytic T cells (Clin Exp Immunol 2002;130:424)
Escape of immune surveillance occurs by inducing apoptosis in CD27+ B and T cells in glioma (Cancer Res 2002;62:2592) and renal cell carcinoma (Neoplasia 2006;8:933); also infection by chronic lymphocyte choriomeningitis virus (J Exp Med 2006;203:2405)
Uses: possibly to differentiate thymic carcinoma (CD70+) from thymoma (CD70-), or to identify clear cell variant of renal cell carcinoma (CD70+)
Micro images: various images
Positive staining (normal): activated B and T cells, monocyte derived dendritic cells (J Leukoc Biol 2004;76:1134)
Positive staining (disease): ALL (Exp Hematol 2005;33:1500), CLL (Blood 1995;85:3556), Hodgkin’s lymphoma (Reed-Sternberg cells), glioma, medulloblastoma, nasopharyngeal carcinoma (Am J Pathol 1995;147:1152), renal cell carcinoma (clear cell type, J Urol 2005;173:2150), thymic carcinoma (AJSP 2000;24:742)
Negative staining: thymoma (most)
References: OMIM 602840
Also known as transferrin receptor
Present on actively proliferating cells; essential for iron transport into proliferating cells (benign and malignant)
Iron bound apotransferrin binds CD71, is internalized to endosome, which becomes acidic; the acidic pH leads to iron release, iron-free apotransferrin is returned to cell surface; surface pH causes iron-free apotransferrin to lose affinity for CD71, is released into circulation, allowing a new cycle to begin
Drawing: transferrin-iron cycle
Major IgA receptor on mesangial cells (J Am Soc Nephrol 2003;14:327)
Uses: high serum levels can diagnose hemolytic anemia (Ann Hematol 2003;82:228) or other anemic conditions; similar to TIBC for differentiating iron deficiency anemia from anemia of chronic disease (AJCP 2001;115:112); not useful for detection of early iron deficiency (Ann Clin Lab Sci 2005;35:435); used to detect micronucleated reticulocytes / Howell-Jolly bodies by flow cytometry (Mutat Res 2003;542:77), also used to test for erythropoietin doping by athletes
Micro images: normal and diseased kidney
Positive staining (normal): all proliferating cells; erythroid precursors through reticulocytes, capillary endothelium in brain
Positive staining (disease): AML M6, anaplastic large cell lymphoma (AJSP 1988;12:264), primary effusion lymphoma (AJCP 1996;105:221); other tumors
References: OMIM 190010
Cell surface protein expressed exclusively on B cells
Regulates mature B cell differentiation, prevents differentiation of naive B cells into plasma cells (Eur J Immunol 2005;35:2325)
Ligand of CD5 (J Immunol 1992;148:1630) and CD100 (Int Immunol 2005;17:1277)
Not the same as DBA.44 (abstract in AJSP 1996;20:613 is apparently wrong)
Increased nucleotide mutation of CD72 mRNA accounts for decreased CD72 expression in B cells of teenage SLE patients (Pediatr Allergy Immunol 2006;17:565)
Uses: marker of B cells (not commonly used)
Positive staining (normal): B cells only
Positive staining (disease): B cell lymphoma
Negative staining: plasma cells (Am J Hematol 1992;41:151)
References: OMIM 107272
Also called ecto-5'-nucleotidase
Catalyzes dephosphorylation of ribo- and deoxyribonucleotides to their corresponding nucleosides, such as 5’ AMP to adenosine
Mediates costimulatory signals in T cell activation
Mediates lymphocyte adhesion to dendritic cells (Blood 1996;88:1755) and endothelium (J Immunol 2000;165:5411)
May protect against vascular inflammation and neointima formation (Circulation 2006;113:2120)
May be a lymphocyte maturation marker
Uses: no significant clinical use by pathologists
Positive staining (normal): B and T cell subset, endothelial cells, follicular dendritic cells, epithelial cells
References: OMIM 29190
Also called LN2, HLA-DR-associated invariant chain
Gamma chain antigen associated with MHC class II antigen and antigen presentation
MHC class II chaperone-stabilizes alpha/beta heterodimers in a complex soon after synthesis, and directs transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place
H. pylori urease binds to CD74 on gastric epithelial cells (Infect Immun 2006;74:1148), and upregulates CD74 expression (J Immunol 2005;175:171)
Has important role in mucosal immunity
Receptor for macrophage migration inhibitory factor, a proinflammatory cytokine (J Immunol 2006;177:8730)
Associated with perineural invasion in pancreatic carcinoma (Clin Cancer Res 2006;12:2419)
Uses: B cell marker (not commonly used)
Micro images: normal tonsil; increased expression in H. pylori+ epithelium #1; #2; multiple myelomas (figures G-J); renal tumors (figures D-F)
Positive staining (normal): B-cells, activated T-cells, macrophages, interdigitating dendritic cells, activated endothelial and epithelial cells
Positive staining (disease): many B cell lymphomas, myeloma (Clin Cancer Res 2004;10:6606), some T cell lymphomas, Reed-Sternberg cells, many myeloid leukemias, Langerhans cell histiocytosis; renal clear cell and chromophobe carcinoma (most, Am J Pathol 2001;158:1639)
Negative staining: renal oncocytoma
References: OMIM 142790
Also called lactosamines, LN-1; formerly CDw75
A carbohydrate, not a protein (Cell 1992;68:1003)
Ligand for CD22 (Cell 1991;66:1133)
A neuraminidase-sensitive lymphocyte cell surface differentiation antigen
Strong expression associated with better prognosis in follicular center cell lymphoma (J Pathol 2006;209:352)
Uses: marker of follicular center cell lymphoma; identify Reed-Sternberg cells (not commonly used)
Micro images: lymphocyte predominance Hodgkin’s lymphoma; marginal zone lymphoma (aberrant expression)-figure 4
Positive staining (normal): mature B cells (germinal center derivation), erythrocytes, some T cells, some epithelial cells,
Positive staining (disease): “popcorn cells” of lymphocyte predominance Hodgkin’s lymphoma, many B cell lymphomas (Histopathology 1999;35:209)
References: Archives 2002;126:862
CD75s
Alpha-2,6-sialylated lactosamines (formerly CDw76)
A carbohydrate, not a protein
Marker of murine CD8+ suppressor T cells (Int Immunol 2003;15:1389)
Uses: no significant clinical use by pathologists
Positive staining: B cells, some T cells
Renamed CD75s at 7th HLDA Workshop
Also called globotriaosylceramide
pK blood group antigen on erythrocytes
A carbohydrate, not a protein
Endothelial receptor for verotoxins (J Biol Chem 2006;281:10230), including from Shigella dysenteriae and E. coli
Also interacts with CD19 (J Cell Physiol 1998;176:281)
Mediates apoptosis of renal vascular endothelial cells and intestinal epithelial cells, resulting in hemolytic uremic syndrome
Does NOT discriminate centroblasts from centrocytes
Also expressed by liver flukes (Biol Chem 2001;382:195)
Uses: identify germinal center cells
Positive staining (normal): B cells (centrocytes, centroblasts, plasmablasts, J Immunol 2006;177:4341), megakaryoblasts and platelets (J Biol Chem 2002;277:11247)
Positive staining (disease): Burkitt's lymphoma
References: OMIM 607922 (CD77 synthase)
Deleted at 7th HLDA Workshop (reasons unknown)
Defines a conformation of MHC class II molecules bound to peptides acquired through trafficking to lysosomal antigen processing compartments, and not MHC class II molecules associated with tetraspanins (J Immunol 2006;177:5451)
Appears on B cells following HLA-DR and preceding CD10, CD19, CD22 and CD37
Uses: no significant clinical use by pathologists
Positive staining (normal): B cells
Also called MB-1, B-cell antigen receptor complex associated protein alpha-chain
Encodes Ig-alpha protein of the B-cell antigen receptor; the receptor also includes Ig-beta protein (CD79b) and surface immunoglobulin
Expressed early in B-cell differentiation (often positive when mature B-cell markers are negative); also expressed in plasma cells
In AML, presence usually represents aberrant B cell antigen in leukemias of distinct myeloid linage, not biphenotypic differentiation (Cancer Genet Cytogenet 2005;163:62)
CLL patients have low B cell-IgM surface expression due to defects in glycosylation and folding in µ and CD79a chains (Blood 2005;105:2933)
Less specific than PAX5 for acute leukemia (Cancer Res 2004;64:7399)
Uses: general detection of B cells/B cell origin (with CD20); also
- in ALL or small B cell lymphoproliferative disorders when CD20 may be negative (AJCP 2006;126:534) or after rituximab (anti CD-20) therapy (AJSP 2005;29:1399)
- in infarcted lymphomas (Archives 2003;127:60)
- to differentiate preB lymphoblastic lymphoma from Ewing’s sarcoma (Mod Path 2001;14:1175)
Micro images: measles
related appendicitis: Warthin-Finkeldey giant cells (figure C); prominent
CD79+ hematogones in fatal Shwachman-Diamond syndrome (figure 2C); follicular dendritic
cell tumor; lymphoplasmacyte
rich meningioma; quality
control
leukemia/lymphoma - infarcted
lymphomas (figures 2 & 6); primary mediastinal
B cell lymphoma; pro B
acute lymphoid leukemia (bottom left); peripheral
T cell lymphomas #1; #2
(figure 2B); T cell
lymphoblastic leukemia (middle right); t(8;21)
myeloid leukemia (bottom right); T
cell lymphoblastic lymphoma with coexisting Langerhans cell histiocytosis
(figure B)
Positive staining (normal): B cells, plasma cells
Positive staining (disease): B cell leukemia / lymphoma (but variable staining in plasmablastic lymphoma and primary effusion lymphoma); nodular lymphocyte predominant Hodgkin’s lymphoma (faint, AJCP 2003;119:192), classic Hodgkin’s lymphoma (18%, Mod Path 2004;17:1531), t(8,21) myeloid leukemias, T cell leukemias/lymphomas (some, AJCP 2000;113:823), primary plasmacytoma of lymph node (Hum Path 1997;28:1083)
Negative staining: anaplastic large cell lymphoma (Hum Path 2004;35:455), granulocytic sarcoma
References: OMIM 112205, Blood 1995;86:1453 (early study)
CD79b
Also called B29, B-cell antigen receptor complex associated protein beta-chain
Encodes the Ig-beta protein of the B-cell antigen receptor; the receptor also includes Ig-alpha protein (CD79a) and surface immunoglobulin
First expressed in cells with Ig µ chains and remains expressed throughout B cell differentiation to plasma cells
Uses: distinguish CLL from other B cell disorders if intensity of staining is considered (J Clin Pathol 2002;55:180)
Flow cytometry images: CLL
Micro images: normal tonsil
Positive staining (normal): B cells, plasma cells
Positive staining (disease): B cell lymphoma and lymphoproliferative disorders - CLL (18%, Archives 2003;127:561), CLL with IgM paraproteins (58%, AJCP 2005;123:594), lymphoplasmacytic lymphoma (85%, AJCP 2005;124:414)
Negative staining: hairy cell leukemia (usually)
References: OMIM 147245
Also called B7-1, BB1
T cells need two signals for activation; the first signal is antigen peptide presented on MHC class II through the T cell receptor
The second (costimulatory) signal is delivered by CD80 or CD86, expressed on surface of antigen presenting cells, which interact with either CD28 or CD152 (CTLA-4)
Has critical role in autoimmune, humoral, and transplant responses
Increased expression may cause excessive antigen presentation in fulminant hepatic failure as an early step in its pathogenesis before the onset of tissue damage (Am J Pathol 1999;154:1711)
Receptor for some adenovirus species (Virus Res 2006;122:144)
Uses: no significant clinical use by pathologists
Diagram: CD80/86 binding and antagonism by drug abatacept
Micro images: normal esophagus; esophageal carcinoma; inflamed skin
Positive staining (normal): activated B cells, T cells, macrophages, dendritic cells
References: OMIM 112203
Also called Target of an Anti-Proliferative Antibody (TAPA1)
Receptor for Hepatitis C Virus E2 protein in B cells (J Virol 2006;80:8695)
Also required for Plasmodium falciparum infectivity (Nat Med 2003;9:93)
Upregulation on HIV1+ B cells may ultimately cause lymphoproliferative disorders (Clin Exp Immunol 2007;147:53)
On B cells, is complexed with CD21, CD19 and Leu13; facilitates complement recognition
Member of tetraspanin family; has close associations with major histocompatibility complex class I/II proteins
Appears to promote muscle cell fusion and support myotube maintenance
Uses: no significant clinical use by pathologists
Positive staining (normal): lymphocytes, endothelial cells, epithelial cells
Positive staining (tumor): HCV+ splenic diffuse large B cell lymphoma (Hum Path 2005;36:878); Burkitt’s lymphoma cell lines, neuroblastoma cell lines (J Pediatr Hematol Oncol 2000;22:20)
Negative staining: erythrocytes, platelets, neutrophils
References: OMIM 186845
Also called prostate cancer antimetastasis gene KAI1, kangai 1 (Chinese for anticancer).
Metastasis suppressor gene
Expression correlates with p53 expression
Reduced expression of CD82 is associated with metastases/poor prognosis in carcinomas of bladder (Int J Urol 2004;11:74), breast (Am J Pathol 1998;153:973, J Cancer Res Clin Oncol 2005;131:191), colon (World J Gastroenterol 2004;10:2245), endometrium (Clin Cancer Res 2003;9:1393), larynx (Lin Chuang Er Bi Yan Hou Ke Za Zhi 2005;19:1065), oral cavity (Clin Cancer Res 2002;8:828), thyroid (Int J Mol Med 2004;14:517, Pathol Res Pract 2003;199:79)
Expression reduces function of urokinase-type plasminogen activator receptor (J Biol Chem 2005;280:14811)
Uses: possible use as prognostic marker (see above)
Micro images: breast carcinoma; colon carcinoma: membranous and cytoplasmic staining #1-HT29 cell lines; #2-SW480 cell lines; #3-colon carcinoma cells; endometrial carcinoma; oral cavity (normal and malignant)
Positive staining (normal): activated/differentiated hematopoietic cells, endothelial cells, epithelium
Negative staining: erythrocytes
References: OMIM 600623
Also called HB15
May assist in antigen presentation or cellular interactions that follow lymphocyte activation.
Soluble form inhibits dendritic cell maturation and inhibits dendritic cell-mediated T cell proliferation (J Med Dent Sci 2006;53:85)
Elevated serum levels seen in mantle cell lymphoma and CLL (Leuk Res 2004;28:237)
Higher number of activated dendritic cells may be good prognostic factor for breast carcinoma (Int J Cancer 2003;104:92), cholangiocarcinoma (Hum Path 2004;35:881), colorectal liver metastases (Hum Path 2004;35:1392), gallbladder carcinoma (Oncol Rep 2005;14:353), gastric carcinoma-EBV+ (AJSP 2006;30:59) and advanced (Oncol Rep 2005;14:369)
Uses: marker for activated dendritic cells
Micro images: decidua; infantile hemangioma endothelium; CD83+ dendritic cells in breast tumor free sentinel lymph node; Churg-Strauss syndrome myocarditis
Positive staining (normal): activated (mature) dendritic cells, activated T and B lymphocytes, monocytes/macrophages (transient, Biochem J 2005;385:85), Langerhans cells, thymic epithelial cells, neutrophils during acute bacterial infection (Clin Exp Immunol 2002;130:501), decidua (Am J Pathol 2000;157:159)
Positive staining (disease): infantile hemangioma endothelium (Am J Pathol 2006;168:621), Reed-Sternberg cells (Pathology 1997;29:294), Churg-Strauss syndrome myocarditis in inflammatory infiltrates (Archives 2003;127:98)
References: OMIM 604534
Also called Signaling Lymphocytic Activation Molecule 5 (SLAM5)
Adhesion molecule that increases proliferative responses of activated T cells (J Immunol 2003;171:2485)
Mediates platelet aggregation (Blood 2005;106:3028)
Uses: no significant clinical use by pathologists
Positive staining (normal): B cells, thymocytes (J Immunol 2001;167:3668), mature T cells, memory T cells (high, Tissue Antigens 2004;64:132), monocytes/macrophages, platelets, dendritic cells, granulocytes and CD34+ hematopoietic progenitor cells (Exp Hematol 2003;31:798)
References: OMIM 604513
Previously entire Immunoglobulin-like Transcript (ILT) family was clustered as CD85; now subclassified as CD85a to CD85m
Also called Leukocyte Immunoglobulin-like Receptors (LIR) and Monocyte/Macrophage Immunoglobulin-like Receptors (MIR)
CD85 itself is now called CD85J (see below)
Family of immunoreceptors expressed on monocytes and B cells; lower levels on dendritic cells and NK cells
Prevents NK / T cell killing and inhibits B cells by negative signaling receptors
Note: some family members have activating functions (see specific family members below)
References: Nature Immunology 2001; 2:661-Nomenclature
CD85A
Also called ILT5, LIR3, LILRB3 (leukocyte immunoglobulin-like receptor subfamily, member 3), HL9
Involved in NK mediated cytotoxicity
An inhibitory receptor for MHC class I molecules
Uses: no significant clinical use by pathologists
Positive staining (normal): myeloid cells, monocytes/macrophages, B cells, T cells (some), NK cells, basophils (Blood 2004;104:2832), eosinophils (Proc Natl Acad Sci USA 2003;100:1174), dendritic cells (weak)
References: OMIM 604820
CD85B
Also called ILT8, LILRA6 (formerly LILRB6)
Involved in the activation of NK-mediated cytotoxicity
Uses: no significant clinical use by pathologists
Positive staining (normal): NK and T cell subsets, monocytes, macrophages, dendritic cells and B lymphocytes
References: Washington State University
CD85C
Also called LIR8, LILRB5
May act as receptor for class I MHC antigens
Uses: no significant clinical use by pathologists
Positive staining (normal): NK cells
References: OMIM 604814
CD85D
Also called ILT4, LIR2, MIR10, LILRB2
Down regulates the immune response; involved in the development of tolerance
Upregulated by HLA-G in antigen-presenting cells, NK cells, and T cells (FASEB J 2005;19:662)
Interacts with human leukocyte antigen A, B, and G molecules and transmits negative signals that interfere with the activation of monocytes and dendritic cells (Hum Immunol 2004;65:700)
Also competes with CD8A for binding to class I MHC antigens
IL-10 renders dendritic cells hypostimulatory by upregulating cell surface CD85D and by inhibiting soluble CD85D in vitro (Eur J Immunol 2004;34:74); similar effect on endothelial cells (Eur J Immunol 2006;37:177)
Uses: no significant clinical use by pathologists
Positive staining (normal): NK cells, T cells, monocytes/macrophages, dendritic cells, eosinophils (Proc Natl Acad Sci USA 2003;100:1174)
References: OMIM 604815
CD85E
Also called ILT6, LIR4, LILRA3
May act as soluble receptor for class I MHC antigens
Homozygous deletions associated with multiple sclerosis (7% vs 4% of normals, Genes Immun 2005;6:445)
85% of Japanese lack functional CD85E alleles (Hum Genet 2006;119:436)
Uses: no significant clinical use by pathologists
Positive staining (normal): B cells, NK cells, peripheral blood monocytes, lung
References: OMIM 604818
CD85F
Also called ILT11, LILRB7, LIR9
May play a role in triggering innate immune responses (Blood 2003;101:1484)
Membrane bound and secreted
Uses: no significant clinical use by pathologists
Positive staining (normal): neutrophils, monocytes
Negative staining: B cells, T cells, NK cells
References: OMIM 606047
CD85G
Also called ILT7, LILRA4
May act as receptor for class I MHC antigens
Uses: no significant clinical use by pathologists
Positive staining (normal): plasmacytoid dendritic cells (J Exp Med 2006;203:1399)
Negative staining: myeloid dendritic cells, other white blood cells
CD85H
Also called ILT1, LIR7, LILRA2
May act as receptor for class I MHC antigens
Activating receptor for eosinophils ((Proc Natl Acad Sci USA 2003;100:1174)
Uses: no significant clinical use by pathologists
Positive staining (normal): basophils (Blood 2004;104:2832), myeloid and plasmacytoid dendritic cells
Negative staining: monocytes, T cells, B cells, NK cells
References: OMIM 604812
CD85I
Also called LIR6
Uses: no significant clinical use by pathologists
Positive staining (normal): B cells, monocytes
Negative staining: dendritic cells, NK cells, T cells
References: OMIM 604810, J Immunol 2003;171:3056
CD85J
Also called CD85, LIR1, ILT2, MIR7, LILRB1
Transduces negative signals that prevent killing of MHC class I expressing cells
Binds classical (HLA-A and -B) and non-classical (HLA-G, -E and -F) MHC class I molecules
Upregulated by HLA-G in antigen-presenting cells, NK cells, and T cells (FASEB J 2005;19:662)
Receptor for CMV UL18 protein, which resembles MHC class I molecules (J Virol 2005;79:2251)
Uses: no significant clinical use by pathologists
Micro images: normal skin (figure C); psoriatric skin (figure D)
Positive staining (normal): B cells, monocytes, dendritic cells (low), T cells (some), NK cells (some)
References: OMIM 604811
CD85K
Also called ILT3, LIR5, HM18, LILRB4
Upregulated by HLA-G in antigen-presenting cells, NK cells, and T cells (FASEB J 2005;19:662)
Receptor for class I MHC antigens
Recognizes broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles
Involved in downregulation of immune response and development of tolerance, including transplants (Int Immunol 2004;16:1055)
Aspirin use is associated with upregulation (Am J Transplant 2006;6:2046)
Uses: no significant clinical use by pathologists
Positive staining (normal): dendritic cells (various, Gene 2004;331:159), monocytes/macrophages (J Exp Med 1997;185:1743), endothelial cells (Transplantation 2006;82:S30)
References: OMIM 604821
CD85L
Also called ILT9, LILRA6P, LILRP1
Uses: no significant clinical use by pathologists
References: Eur J Immunol 1998;28:3959
CD85M
Also called ILT10, LILRA5
Uses: no significant clinical use by pathologists
Positive staining (normal): T cell subsets, monocytes, macrophages, neutrophils, dendritic cells and B lymphocytes (Washington State University)
References: J Biol Chem 2006;281:19536
Also called B7-2
T cells need two signals for activation - the first signal is antigen peptide presented on MHC class II through the T cell receptor
The second (costimulatory) signal is delivered by CD80 or CD86, expressed on surface of antigen presenting cells, which interact with either CD28 or CD152 (CTLA-4)
CD80 and CD86 appear to have opposing functions on regulatory T cells (J Immunol 2004;172:2778)
Polymorphisms are associated with liver transplant acceptance (Transpl Immunol 2005;15:69) and systemic sclerosis (Int J Immunogenet 2006;33:155)
Increased expression may cause excessive antigen presentation in fulminant hepatic failure as an early step in its pathogenesis before the onset of tissue damage (Am J Pathol 1999;154:1711)
High circulating soluble levels are poor prognostic factor in myeloma (Br J Haematol 2006;133:165); are associated with severe asthma (Thorax 2004;59:870)
Receptor for some adenovirus species (Virus Res 2006;122:144)
Associated with H. pylori dependent early stage high grade MALT lymphoma of stomach (World J Gastroenterol 2005;11:4357)
Uses: no significant clinical use by pathologists
Micro images: inflamed skin; fulminant hepatic failure; chronic HBV infection of liver; liver sinusoidal endothelial cells; thyroid carcinoma (E-H); normal esophagus; esophageal carcinoma
early stage high grade gastric MALT lymphoma - H. pylori dependent case (CD86+); H. pylori independent case (CD86-)
Positive staining (normal): interdigitating dendritic cells in T zones of secondary lymphoid organs, Langerhans cells, peripheral blood dendritic cells, memory B cells, germinal center B cells, monocytes, endothelial cells, activated T cells
Positive staining (disease): AML (29%, Clin Cancer Res 2005;11:5708), ulcerative colitis (100%, Dig Dis Sci 2004;49:1738)
Negative staining: immature dendritic cells
References: OMIM 601020
Also called urokinase plasminogen activator receptor (uPA-R), PLAUR
Membrane protein responsible for plasmin expression on cells
Binds both the proprotein and mature forms of urokinase plasminogen activator
Subject to negative feedback regulation by uPA, which cleaves it to an inactive form
Implicated in metastasis - receptors for uPA and plasmin are found at leading edge of tumor cells; plasmin causes hydrolysis of extra-cellular matrix proteins in the path of cellular invasion
Plasma levels of different soluble receptors are increased and predict mortality in HIV patients (J Acquir Immune Defic Syndr 2005;39:23)
Pre-storage leukofiltration reduces transfusion reactions, perhaps due to reduction in soluble CD87 (Transfus Med 2004;14:305)
Hypoxia (Exp Mol Med 2004;36:57) and glucose deprivation (Exp Cell Res 2006;312:1685) may induce tumor invasion and metastases by upregulating CD87
Upregulated by dialysis, and associated with clinical findings (Blood Purif 2006;24:236)
Receptor for Group A Streptococcus (J Mol Biol 2005;350:27)
Uses: no significant clinical use by pathologists
Micro images: breast carcinoma (figure A); breast carcinoma and fibroadenoma; endometrial adenocarcinoma #1; #2; pancreatic adenocarcinoma (figures B, D)
Positive staining (normal): T-cells, NK cells, monocytes / macrophages, bands and neutrophils (Cytometry B Clin Cytom 2003;51:9), endothelial cells, fibroblasts, basophils (J Immunol 2004;173:5739), smooth muscle cells, keratinocytes, placental trophoblasts, hepatocytes
Positive staining (tumors): carcinomas of breast (Am J Pathol 2000;157:1219), colon and prostate; prostatic nodal metastases (Hum Path 2006;37:1442), melanoma, malignant and benign primary CNS tumors (Appl Immunohistochem Mol Morphol 2005;13:184)
Negative staining: normal prostate, B/T cells and Hodgkin’s lymphoma (AJCP 1994;102:835)
References: OMIM 173391, Wikipedia
Also called C5R1, C5aR
Receptor for C5a, the chemotactic and inflammatory peptide anaphylatoxin
Stimulates chemotaxis, granule enzyme release and superoxide anion production
May potentiate leukotriene production in lung and contribute to inflammation in asthma (Microbiol Immunol 2005;49:981), but also protects against airway hyperresponsiveness (J Clin Invest 2006;116:783)
May also be involved in pathogenesis of COPD (Am J Respir Cell Mol Biol 2004;31:216)
CD87 may mediate upregulation of CD88 in glomerular mesangial cells (J Cell Sci 2005;118:2743) but see Nephrol Dial Transplant 2000;15:1888
Reduced levels on neutrophils in HIV patients (J Infect Dis 2001;183:662)
CD88 antagonists may be useful for treating complement mediated disorders (J Biomed Biotechnol 2006;2006:28945, J Immunol 2005;174:783)
Diagram: C5A and its effects
Uses: no significant clinical use by pathologists
Micro images: normal and Alzheimer’s brain #1; #2; kidney
Positive staining (normal): granulocytes, macrophages/monocytes, dendritic cells, mast cells (variable, J Allergy Clin Immunol 2005;115:1162), eosinophils (Eur J Immunol 1996;26:1560), endothelial cells, hepatocytes, reactive astrocytes and microglia (Am J Pathol 1997;150:31), keratinocytes in inflamed skin (Am J Pathol 1999;154:495)
Positive staining (disease): synoviocytes in arthritis (Chin Med J (Engl) 2003;116:1408), mast cell sarcoma (AJSP 2003;27:1013)
References: OMIM 113995
Also called FCAR, FCalphaR
IgA Fc receptor, binds IgA and eliminates IgA coated targets
Induces phagocytosis, degranulation, respiratory burst and killing of microorganisms
Pathogenic group A and group B streptococci produce virulence factors that block the binding of IgA to CD89, inhibiting IgA-mediated immunity. (J Biol Chem 2006;281:1389)
Uses: no significant clinical use by pathologists
Positive staining (normal): neutrophils, monocytes/macrophages, activated eosinophils, alveolar and splenic macrophages, interstitial dendritic cells
Negative staining: mesangial cells (J Am Soc Nephrol 2000;11:241)
References: OMIM 147045
Also called Thy-1
May mediate differentiation of hematopoietic stem cells and synaptogenesis in the CNS
CD34+ CD90+ cells include hematopoietic stem cells that serve as autologous grafts to replace the bone marrow in patients with malignancies (Biol Blood Marrow Transplant 2000;6:262)
Mediates adhesion of various white blood cells to activated endothelial cells (J Immunol 2004;172:3850)
Uses: hematopoietic stem cell marker
Micro images: normal and diseased skin; prostatic adenocarcinoma; myometrial and endometrial fibroblasts
Positive staining (normal): immature hematopoietic stem cells, neurons, connective tissue, activated endothelial cells, fibroblasts (variable, Am J Pathol 2003;163:1291), keratinocyte stem cells (Br J Dermatol 2006;154:1062)
Positive staining (disease): Ewing’s sarcoma and some rhabdomyosarcomas (AJCP 2003;119:643)
References: OMIM 188230, Wikipedia
Low density lipoprotein receptor-related protein 1 (LRP1); also called alpha-2-macroglobulin receptor
Large scavenger receptor that mediates the uptake and degradation of various ligands
Binds to apoE-containing lipoproteins and mediates chylomicron remnant clearance from the plasma
May suppress thyroid carcinoma invasion by clearing urokinase plasminogen activator (Int J Biochem Cell Biol 2006;38:1729)
Increased CD91 surface expression on CD14(+) monocytes is associated with the apparent HIV1 resistance observed in HIV exposed but seronegative subjects (J Leukoc Biol 2005;78:37)
Increased expression on monocytes in melanoma patients is associated with slow progression (Clin Exp Immunol 2004;138:312)
Part of pathway of C1q-mediated apoptotic clearance (Arthritis Rheum 2006;54:1543)
Also a cell surface receptor for heat shock protein gp96 and others (Archives 2003;127:178)
Uses: no significant clinical use by pathologists
Micro images: psoriasis
Positive staining (normal): fibroblasts, dendritic cells (Immunobiology 2006;211:407), macrophages; liver, brain, lung
References: J Thromb Haemost 2005;3:1884, OMIM 107770
Also called choline transporter-like protein 1 (CTL1), Solute carrier family 44 member 1 (SLC44A1)
Produces membrane lipid phosphatidylcholine (Exp Biol Med (Maywood) 2006;231:490)
Uses: no significant clinical use by pathologists
Positive staining (normal): B cells, T cells (most), monocytes, NK cells (some), neutrophils, fibroblasts (weak), endothelial cells
References: OMIM 606105, J Immunol 2001;167:5795
Also called complement component C1q receptor, C1qR
No longer believed to be part of receptor complex for C1q (J Immunol 2002;168:5222)
Enhances phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens
Also enhances phagocytosis via mannan-binding lectin, an important part of the innate immune defense (J Biol Chem 2001;276:43087)
Receptor for pulmonary surfactant protein A
Has role in intercellular adhesion
Soluble form present in plasma (J Immunol 2005;175:1239)
Uses: no significant clinical use by pathologists
Micro images: various images #1; #2; liver (figure 6B)
Positive staining (normal): granulocytes, monocytes, platelets, endothelial cells (J Leukoc Biol 2001;70:793), microglia (J Immunol 2001;166:7496), stem cells (rare, Proc Natl Acad Sci USA 2002;99:10441)
Negative staining: lymphocytes
References: OMIM 120577
Also called natural killer cell antigen, kP43, killer cell lectin-like receptor subfamily D member 1, KLRD1
Receptor for MHC class I HLA-E molecules present on NK cells and some cytotoxic T-cells
Inhibits NK cell activation by disrupting the actin network where the NK cell contacts its ligand (J Immunol 2006;177:3590)
Increased numbers of CD94+ NK cells in active and inactive ulcerative colitis (Hepatogastroenterology 2001;48:1316); increased number of CD94+ T cells in chronic plaque psoriasis (Br J Dermatol 2006;155:318)
Uses: NK cell marker; favorable prognostic marker for lymphoblastic lymphoma (Blood 2005;106:3567), nasal-type, extranodal NK/T cell lymphoma (Blood 2003;102:2623)
Micro images: normal tonsil; nasal-type, extranodal NK/T cell lymphoma (figure C); psoriasis-symptomless skin (figure A)
Positive staining (normal): NK cells, CD8+ T cells
Positive staining (disease): T-cell large granular lymphocyte leukemias (AJCP 2005;124:937)
References: OMIM 602894
Also called Fas, Apo-1, TNF receptor superfamily member 6, TNFRSF6
Cell surface membrane receptor that activates apoptotic pathways when bound by Fas ligand (FasL, CD178)
Extrinsic pathway: activation leads to assembly of a death inducing signaling complex (DISC) consisting of CD95, the Fas-associated death domain (FADD) adapter protein, the initiator caspase-8 (previously called FLICE or MACH) and cellular FLICE inhibitory protein (cFLIP), a regulatory protein that can block or promote autoproteolytic conversion of pro-caspase-8 to caspase-8 within the DISC. Caspase 8 activates a cascade of caspases that ultimately activates caspase 3, which mediates apoptosis
Intrinsic pathway: involves release of cytochrome c from mitochondria, which complexes with apoptosis inducing factor 1, procaspase 9 and ATP, leading to caspase 9 activation, which activates caspase 3
Fas-FasL system mediates extra-thymic self-tolerance (FasL+ cells induce apoptosis in infiltrating Fas+ lymphocytes in testis, cornea), T cell mediated cytotoxicity, apoptosis during development, halting of immune response
Defects in Fas-Fas ligand pathway (usually Fas but occasionally FasL germline mutations) cause autoimmune lymphoproliferative syndrome, a rare childhood disorder associated with B cell lymphomas, classic Hodgkin’s lymphoma and nodular lymphocyte predominant Hodgkin’s lymphoma, Leuk Lymphoma 2004;45:423
CD95 downregulation may reduce CD4+ T cells in HIV (Archives 2002;126:28)
May be involved in clearance of benign ovarian epithelial inclusion cysts; derangement in pathway may cause ovarian surface epithelial carcinomas (Hum Path 2005;36:971)
Polymorphisms in Fas or FasL: associated with increased risk of autoimmune hepatitis (Am J Gastroenterol 2005;100:1322), increased risk of type II diabetes (Genes Immun 2006;7:316); Fas -670 AG genotype is associated with increased risk of preterm premature rupture of membranes (Am J Obstet Gynecol 2005;193:1132); Fas -670 AA genotype is associated with reduced liver graft survival (Tissue Antigens 2006;67:117); FAS -1377AA genotype is associated with increased risk of lung cancer (J Med Genet 2005;42:479)
Prognostic factors: reduced Fas expression is a poor prognostic factor for breast carcinoma (Clin Cancer Res 2004;10:1360), colorectal carcinoma (Carcinogenesis 2006;27:1113), retinoblastoma (Ocul Immunol Inflamm 2003;11:107) and urothelial carcinoma (Br J Cancer 2005;93:544), but reduced Fas expression is a favorable prognostic factor in primary nodal diffuse large B cell lymphoma (Am J Hematol 2006;81:307) and subcutaneous panniculitis-like lymphoma (AJCP 2004;121:408)
Apoptosis pathways: cytotoxic T lymphocyte pathway #1; #2; initial events; apoptosis pathway chart
Uses: prognostic factors (above)
Micro images: normal kidney (FasL-left, Fas-right); chronic gastritis; lymph node of HIV patient
malignancies - extrahepatic bile duct carcinoma (figures C-H); gastric MALT lymphoma; renal cell carcinoma (FasL-left, Fas-right)
Positive staining (normal): activated B cells, activated T cells (initially extra but nonfunctional Fas), resting T cells (low levels), numerous epithelium and connective tissue
Positive staining (disease): Barrett’s esophagus (Hum Path 2002;33:686), Hashimoto’s thyroiditis (thyroid epithelial cells), ovarian cystadenoma and serous borderline tumors, Reed-Sternberg cells in classic Hodgkin’s lymphoma (AJSP 2001;25:388)
Negative staining: invasive ovarian carcinoma
References: OMIM 134637
Also called T cell activated increased late expression (TACTILE)
May be involved in adhesion of activated T and NK cells late in immune response
Binds CD155
Uses: no significant clinical use by pathologists
Positive staining (normal): activated T cells and NK cells, B cells (low levels)
Positive staining (disease): T-ALL (Exp Hematol 1998;26:1209)
References: J Immunol 2004;172:3994, OMIM 606037
Binds to CD55 and G protein-coupled receptors
May be involved in cell adhesion and signaling processes early after leukocyte activation
May be involved in migration of neutrophils (J Immunol 2004;172:1125)
Highly expressed at sites of inflammation in skin, lung and rheumatoid arthritis
May contribute to angiogenesis associated with tumors (Blood 2005;105:2836)
Glycosylation causes CD97 to show two different epitopes, EGF and Stalk (Int J Cancer 2004;112:815)
Uses: no significant clinical use by pathologists
Micro images: normal oral mucosa; colorectal carcinoma; gastric carcinoma; oral squamous cell carcinoma; thyroid carcinoma; thyroid (various)
Positive staining (normal): activated T > B cells, monocytes/macrophages, dendritic cells, granulocytes, smooth muscle cells
Positive staining (disease): GI carcinomas (Oncol Rep 2005;14:1413, AJCP 2002;118:699), thyroid carcinoma (stronger if undifferentiated, J Clin Endocrinol Metab 1999;84:1104)
Negative staining: microglia
References: Tissue Antigens 2001;57:325, OMIM 601211
Also called SLC3A2
Heavy chain of amino acid transporters (J Cell Sci 2005;118:889)
Involved in cell fusion necessary for syncytiotrophoblast formation (J Physiol 2003;550:3)
Strongly expressed by neoplastic cells; expression contributes to transformation by promoting anchorage- and serum- independent growth (J Biol Chem 2004;279:54731)
Uses: no significant clinical use by pathologists
Micro images: placenta
Positive staining (normal): broad
Positive staining (tumors): all tumor cells
References: OMIM 158070
Also called MIC2, O13, T cell surface glycoprotein E2
Encoded by pseudoautosomal gene on short arms of X and Y
Part of Xg blood group system (website)
Functions: cell surface glycoprotein involved with (a) differentiation of primitive neuroectodermal cells (Exp Mol Med 2003;35:438), (b) apoptosis of T cells (FEBS Lett 2003;554:478), (c) T cell adhesion, (d) migration of leukocytes, (e) in Ewing’s/PNET, may promote growth and migration of tumor cells via downregulation of KCMF1 (potassium channel modulatory factor), a possible metastasis suppressor gene (Oncogene 2006;25:2795)
Associated with EWS-FLI1 fusion transcript, t(11;22)(q24;q12), causing FLI-1 protein overexpression
Interpretation: distinct membranous staining for Ewings/PNET; cytoplasmic for other tumors
Uses: relatively non-specific marker for Ewing’s sarcoma and T cell lymphoma, but does distinguish Ewing’s from neuroblastoma (Hum Path 1993;24:880); also distinguishes meningeal hemangiopericytoma (CD99+) from anaplastic meningiomas (CD99 weak/focal/negative, Hum Path 2004;35:1413); detect minimal residual disease by CD99+ flow cytometry in T-ALL (Leukemia 2004;18:703); anti-CD99 antibody may have therapeutic value (Eur J Cancer 2006;42:91)
Micro images:
Ewing’s/PNET- bone #1; #2 (figure E); cavernous sinus (figure 4); cervix; gallbladder (figure 4A); lung (figure 2); prostate (figure 4); stomach (figure 6); various images; site unknown (figure C)
Leukemia/lymphoma - AML (figures 2C/2D); AML-M0; AML-M3 (figures 3C/3D); anaplastic large cell lymphoma (figures 1D & 1E); chloroma
Other - adult granulosa cell tumor of ovary (figure 4); ectopic hamartomatous thymoma (figure 3A); gastric carcinoma; GIST vs. solitary fibrous tumor; pleomorphic carcinoma of lung (figures 2A-D), solitary fibrous tumor #1 (larynx-figure 6); #2 (ear-figure 2e); spindle cell epithelioma of vagina (figure 4); synovial sarcoma of lung (figure 1c)
Micro images (Mod Path subscribers): PNET of dura (figure C)
Positive staining (normal): endothelial cells, ependymal cells, hepatocytes, gastric foveolar epithelium, immature (cortical) thymic lymphocytes (AJSP 1995;19:1115), ovarian granulosa cells, pancreatic islet cells, Sertoli cells, T cells and activated B cells (J Korean Med Sci 1999;14:600)
Positive staining (tumors):
Ewing's sarcoma/PNET: 100% (AJSP 2005;29:1025); membranous staining (Mod Path 2006;19:659), including tumors of kidney (AJSP 2002;26:320), pancreas (AJSP 2002;26:1040), skin (AJSP 1998;22:310), vulva/vagina (Int J Gynecol Path 2000;19:103); initial report (AJSP 1994;18:486)
leukemia/lymphoma - acute lymphoblastic lymphoma (B and T, AJCP 2001;115:11, J Korean Med Sci 2005;20:952), anaplastic large cell lymphoma (50%), other lymphomas (occasionally), acute myelogenous leukemia/chloroma (50%, Archives 2006;130:153, Mod Path 2000;13:452), leukemia cutis (Mod Path 1997;10:283)
Other - adamantinoma of ulna (Clin Orthop Relat Res 2003;408:256)
angiomatoid MFH (Hum Path 1999;30:1336)
atypical fibroxanthoma (73%, AJCP 2002;117:126)
breast metaplastic carcinoma (Histopathology 2001;39:578)
calcifying aponeurotic fibroma (Hum Path 1998;29:1504)
cervicovaginal myofibroblastoma (Pathology 2005;37:144)
desmoplastic small round cell tumor (23%, AJSP 2002;26:823)
ectopic hamartomatous thymoma (Archives 2003;127:e378)
endometrial stromal tumors with sex cord differentiation
ependymoma (diffuse, strong membranous staining with intracytoplasmic dots, Appl Immunohistochem Mol Morphol 2001;9:125)
epithelioid sarcoma (proximal type-25%, Mod Path 2001;14:655)
extrarenal malignant rhabdoid tumor
gastric carcinoma, intestinal type (some, J Korean Med Sci 2002;17:483)
gastrointestinal stromal tumor (Archives 2002;126:1189)
giant cell angiofibroma (AJSP 2000;24:971)
hemangiopericytoma (meningeal, lipomatous- Hum Path 2000;31:1108)
hepatocellular carcinoma (Indian J Path Microbiol 2003;46:625)
malignant fibrous histiocytoma (35%, J Cutan Pathol 2006;33:24)
melanoma (60%, J Cutan Pathol 2006;33:663)
Merkel cell carcinoma of skin (crisp membranous staining, Appl Immunohistochem Mol Morphol 2000;8:37)
mesenchymal chondrosarcoma (Hum Path 1996;27:1273)
neuroendocrine tumors (Virchows Arch 2000;437:270)
nuchal fibromas
ovarian sex cord stromal tumors (most, AJSP 2005;29:143, Archives 2000;124:563)
ovarian surface epithelial tumors, carcinoids and Wolffian tumors (various)
pancreatic endocrine neoplasms (50%, Histopathology 2004;45:384)
perineuroma (myxoid sclerosing type)
pleomorphic hyalinizing angiectatic tumor (focal, Path Int 2002;52:664)
pulmonary pleomorphic (sarcomatoid) carcinoma (J Korean Med Sci 2005;20:50)
retinoblastoma (focal in 30%, Ann Diagn Path 2001;5:148)
rhabdomyosarcoma (15-25%, Oral Oncol 2002;38:450; AJSP 2002;26:1175)
sclerosing perineuroma (60%-AJSP 1997;21:1433)
sinonasal undifferentiated carcinoma (14%, AJSP 2001;25:156)
skin solitary sclerotic fibroma (J Cutan Path 2003;30:631)
solitary fibrous tumor: myxoid- Mod Path 1999;12:463, oral soft tissue-AJSP 2001;25:900, thyroid gland-AJSP 2001;25:1424, atypical/malignant tumors-60%-AJSP 1998;22:1501
spindle cell epithelioma of vagina (Archives 2001;125:547)
superficial acral fibromyxoma (Hum Path 2001;32:704)
synovial sarcoma (90-100%, all types, AJSP 2002;26:1434)
testicular sex cord stromal tumors (variable- Hum Path 2000;31:1055)
uterine tumors resembling ovarian sex cord tumors (57%, AJSP 2002;26:403)
Wilm’s tumors (some),
Negative staining: clear cell sarcoma, myelodysplastic syndrome, neuroblastoma (children-AJSP 1998;22:327, adults-AJSP 2001;25:918; olfactory-AJSP 1998;22:391, Hum Path 1995;26:639), small cell carcinoma, smooth muscle tumors, squamous cell carcinoma of skin, thymic carcinoma (AJSP 1997;21:936), Wilm’s tumor
References: AJSP 2002;26:1040 (PNET-pancreas), Mod Path 2002;15:673 (PNET-dura), OMIM 313470
Also called SEMA4D, semaphorin 4D
Integral membrane protein and ligand for CD72 and plexin-B1
Functions:
(a) regulates axonal growth cone guidance in the developing CNS through its receptor plexin-B1, which may be related to its expression in invading islands of transformed epithelial cells (but not normal and noninvasive dysplastic epithelium, Proc Natl Acad Sci USA 2006;103:9017)
(b) evokes angiogenic responses from endothelial cells (Blood 2005;105:4321)
(c) impairs monocyte migration
(d) after vascular injury, platelet associated CD100 binds to CD100 receptors on nearby platelets to promote thrombus formation (Proc Natl Acad Sci USA 2007;104:1621)
(e) increases CD45 induced T cell adhesion
(f) down regulates B cell expression of CD23
Expression may have prognostic value in soft tissue sarcoma (Cancer 2007;110:164)
Uses: no significant clinical use by pathologists
Positive staining (normal): most hematopoietic cells including platelets, increased expression after T cell activation
Negative staining: immature bone marrow cells
Micro images: head and neck squamous cell carcinoma
References: OMIM 601866, Wikipedia (semaphorins)
Also called immunoglobulin superfamily member 2 (IGSF2), V7
Inhibits T cell activation induced by CD3, by (a) inhibiting IL-2RA expression on activated T cells and IL2 secretion (J Immunol 1998;161:209), (b) inducing IL10 production (Eur J Immunol 2000;30:3132)
Uses: no significant clinical use by pathologists
Positive staining (normal): monocytes, granulocytes, dendritic cells, activated T lymphocytes in small intestine
Positive staining (disease): CD4+ CD56+ blastic tumor cells (J Invest Dermatol 2005;124:668), Langerhans cell histiocytosis (Histopathology 2000;36:229)
Micro images: CD4+ CD56+ blastic tumor cells
References: OMIM 604516, J Immunol 1998;161:2780
Also called ICAM-2
Binds the leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18)
Provides costimulatory signal in immune response; important in lymphocyte recirculation (J Immunol 2003;171:2588)
Endothelial ICAM-2 mediates angiogenesis (Blood 2005;106:1636)
Elevated serum levels in (a) hemorrhagic fever with renal syndrome (Viral Immunol 2006;19:565) and (b) idiopathic pulmonary fibrosis (Inflammation 2004;28:359)
Uses: no significant clinical use by pathologists
Positive staining (normal): resting lymphocytes, monocytes, platelets, vascular endothelial cells
Positive staining (disease): some lymphomas
Negative staining: neutrophils
References: OMIM 146630
Also called human mucosal lymphocyte antigen 1, integrin alpha E beta 7
CD103+ tumor infiltrating lymphocytes have a cytotoxic antitumor effect (J Exp Med 2007;204:559), may play a role in renal allograft rejection (Am J Transplant 2004;4:1026, J Exp Med 2002;196:873)
Uses: marker for hairy cell leukemia, intraepithelial lymphocytes (normal or tumor)
Positive staining (normal): intraepithelial T lymphocytes (90% in GI, tonsil-J Immunol 2005;175:4355, 30% in lung-Clin Exp Immunol 2007;149:162), lamina propria T lymphocytes in the intestine (50%), dendritic cells in gut (J Exp Med 2005;202:1051), rare peripheral blood lymphocytes
Positive staining (disease): hairy cell leukemia (usually, AJCP 2006;125:251), enteropathy-associated T cell lymphoma, splenic marginal zone lymphoma (some)
Flow cytometry images: hairy cell leukemia variant often expresses CD103 but not CD25 #1; #2 (fig C)
References: OMIM 604682
Also called integrin beta 4 chain
Tends to associate with alpha 6 subunit (CD49f)
Adhesion receptor (for laminins) in normal epithelia that plays a critical role in structure of hemidesmosomes; associated with intermediate filaments
May contribute to tumor progression (Cancer Metastasis Rev 2005;24:413) via VEGF stimulation (J Cell Biol 2002;158:165)
Overexpressed in pancreatic adenocarcinoma (J Histochem Cytochem 2005;53:799)
Mutations are associated with epidermolysis bullosa with pyloric atresia (Exp Dermatol 2004;13:61)
Uses: no significant clinical use by pathologists
Positive staining (normal): epithelium, thymocytes, Schwann cells
Positive staining (disease): carcinomas (some)
Micro images: normal pancreas and adenocarcinoma
References: OMIM 147557
Also called endoglin
Regulatory component of TGF-beta receptor complex; mediates cellular response to TGF-beta 1
Mutations cause Hereditary Hemorrhagic Telangiectasia type I (Am J Hum Genet 1997;61:68)
Required for hemangioblast and early hematopoietic development (Development 2007;134:3041)
Uses: specific and sensitive marker for tumor angiogenesis (better than CD31)
Poor prognostic factor - increased microvessel staining: acute lymphoblastic leukemia in children (Leuk Res 2007 Jun 15; [Epub ahead of print]), breast carcinoma (AJCP 2003;119:374, including node negative-Hum Path 2004;35:176), chronic idiopathic myelofibrosis (Mod Path 2004;17:1513), colorectal carcinoma (Mod Path 2004;17:197), endometrial carcinoma (Gynecol Oncol 2006;103:1007), esophageal adenocarcinoma (Hum Path 2006;37:861), gastric carcinoma (Hum Path 2006;37:861), hepatocellular carcinoma (BMC Cancer 2006;6:110), meningioma (Acta Neuropathol (Berl) 2007;114:147), ovarian carcinoma (Int J Gynecol Cancer 2006;16:1789), primary CNS lymphoma (J Neurooncol 2007;82:249), prostate adenocarcinoma (AJCP 2007;127:572), squamous cell carcinoma of head and neck (Virchows Arch 2006;448:768), including tongue (Laryngoscope 2006;116:1175)
Poor prognostic factor - other: serum endoglin is associated with intrauterine growth restriction during pregnancy (J Clin Endocrinol Metab 2007;92:2831), preeclampsia (N Engl J Med 2006;355:992, Nat Med 2006;12:642), diabetic retinopathy (J Cell Mol Med 2005;9:692)
Tissue endoglin is associated with progressive hepatic fibrosis in chronic HCV infection (J Viral Hepat 2006;13:625) and aortic atherosclerosis (J Atheroscler Thromb 2006;13:82)
Positive staining (normal): activated monocytes, erythroid precursors in marrow; syncytiotrophoblast, cytotrophoblast in first trimester (transient expression)
Positive staining (disease): endometriosis (Reprod Biol 2005;5:51), tumor microvessels (Rom J Morphol Embryol 2007;48:41)
Negative staining: normal endothelial cells (or weak)
Micro images: chronic idiopathic myelofibrosis (fig c, e, f); endometriosis (fig 3-5); liver-normal liver (fig 4); hepatocellular carcinoma #1; #2 and normal liver; lung-non small cell carcinoma (fig D)
References: J Transl Med 2004;2:18
Also called VCAM-1 (vascular cell adhesion molecule 1); alpha 4 beta 1 ligand
Interacts with beta 1 integrin VLA4
Adhesion molecular in activated endothelium; plays a role in migration of white blood cells (J Exp Med 2006;203:2763)
May mediate endothelial progenitor cell recruitment to rheumatoid arthritis synovium (Arthritis Rheum 2007;56:1817); associated with type II rheumatic disease (Cell Mol Biol (Noisy-le-grand) 2002;48 Online Pub:OL243)
Important in initiation of atherosclerosis (J Clin Invest 2001;107:1255)
Renal cell carcinoma may exploit VCAM-1 overexpression for immune system escape (Cancer Res 2007;67:6003); on the other hand, down regulation in breast cancer is associated with nodal metastases (Pathol Oncol Res 2002;8:125)
Increased expression: in placentas of women with pregnancy induced hypertension complicated by intrauterine growth restriction (Di Yi Jun Yi Da Xue Xue Bao 2002;22:1022)
Increased plasma levels: associated with: breast cancer [high stage] with circulating cancer cells (Neoplasma 2006;53:538), cancer (general)-early stage or preclinical (Eur J Cancer 2005;41:2355), dengue virus infection severity (J Med Virol 2004;72:445), diabetes with poor control (high HbA1c-Diabetes Care 2007;30:159 or arteriosclerosis obliterans-Clin Chim Acta 2007;377:198), endometriosis-advanced (J Soc Gynecol Investig 2002;9:98), sickle cell trait in athletes (J Appl Physiol 2007;102:169)
Uses: marker of endothelial damage (Endothelium 2006;13:335)
Positives staining (normal): activated endothelial cells, lymphocytes, monocytes, neural cells, hematopoietic cells
Positive staining (disease): renal cell carcinoma
Micro images: squamous cell carcinoma-well differentiated
References: OMIM 192225
Also called lysosome associated membrane protein 1 (LAMP-1)
Note: DC-LAMP is CD208
Functions:
(a) surface antigen transiently present on cell surface of CD8+ T cells after release of cytolytic granules (J Immunol Methods 2003;281:65)
(b) basophil activation antigen (Cell Res 2005;15:325)
(c) expression correlates with aggressiveness of melanocytic neoplasms (Melanoma Res 2006;16:235)
(d) critical to phagosomes acquiring microbicidal capabilities (Cell Microbiol 2007 May 15; [Epub ahead of print])
(e) ligand to E-selectin mediated cell adhesion
Uses: defective CD107a surface expression discriminates between genetic subtypes of familial hemophagocytic lymphohistiocytosis (Blood 2006;108:2316); used to measure degranulation in CD8+ T cells by flow cytometry (Nat Med 2003;9:1377) and NK cell activity / cytolytic capacity (J Immunol Methods 2004;294:15)
Positive staining (normal): primarily endosome-lysosome membranes, 1-2% on plasma membrane; degranulated platelets (Blood Coagul Fibrinolysis 2003;14:249-53), activated neutrophils, T cells, endothelium
Diagrams: structure
References: OMIM 153330
CD107b
Also called lysosome associated membrane protein 2 (LAMP-2)
X linked
Major constituent of lysosomal membranes (also LAMP-1)
Functions:
(a) mutations cause Danon disease, a lysosomal glycogen storage disease with cardiomyopathy in adult women and men before age 20 years (N Engl J Med 2005;352:362, Circulation 2005;112:1612), Wolff-Parkinson-White syndrome, myopathy, variable mental retardation and retinopathy (Arch Ophthalmol 2007;125:231); skeletal and cardiac muscle cells have intracytoplasmic vacuoles containing glycogen and autophagic material
(b) levels decrease with age (J Cell Sci 2007;120:782)
(c) binding of substrates to LAMP-2 is limiting step in chaperone-mediated autophagy, a selective mechanism for the degradation of soluble cytosolic proteins in lysosomes (EMBO J 2006;25:3921)
(d) may be involved in infection induced involution of thymus via autophagy (Acta Biol Hung 2006;57:315)
(e) facilitates MHC class II presentation of cytoplasmic antigens (Immunity 2005;22:571)
(f) basophil activation antigen (Cytometry A 2004;61:62)
Uses: help differentiate cardiomyopathy due to Danon disease (LAMP-2 negative) from other causes (LAMP-2+, Intern Med 2007;46:757)
Positive staining (normal): lysosome membranes of various tissues, platelets (Thromb Haemost 1996;75:623)
Negative staining: cardiac and skeletal muscle in Danon disease (Neuromuscul Disord 2003;13:708)
Diagrams: structure
Micro images: loss of LAMP-2 in hypertrophic cardiomyopathy patient #1 with Danon disease (fig A, B); #2 (fig A); #3 (loss of staining in muscle and heart); LAMP2+ cardiac myocytes in non Danon disease cardiomyopathy (fig 1g)
References: OMIM 309060
Also called semaphorin 7A (SEMA7A) or John-Milton-Hagen (JMH) human blood group antigen
A semaphorin (Wikipedia)
Receptors are plexin C1 and beta1 integrins
Functions:
(a) genetic variations may play a role in decreased bone mineral density and risk of vertebral fracture (J Hum Genet 2006;51:112)
(b) extremely potent monocyte activator; stimulates chemotaxis and cytokine production (Scand J Immunol 2002;56:270)
(c) stimulates axon growth and guidance during development (Nature 2003;424:398)
(d) negative regulator of T cell responses (Immunity 2006;24:591)
(e) expression is correlated with the establishment of dentin-pulp complex terminal innervation (Matrix Biol 2005;24:232)
Positive staining (normal): erythrocytes, activated lymphocytes, odontoblasts, monocytes, keratinocytes, fibroblasts
References: OMIM 607961
Also called Platelet activation factor
Glycosylphosphatidylinositol-anchored cell surface protein
Carries the biallelic platelet-specific Gov antigen system; alloantibodies to HPA-15 residing on CD109 are implicated in refractoriness to platelet transfusion, fetal/neonatal alloimmune thrombocytopenia and posttransfusion purpura (Blood 2002;99:1692)
Positive staining (normal): activation antigen for platelets and T cells; subset of hematopoietic stem and progenitor cells (Exp Hematol 1999;27:1282); myoepithelial cells (breast, prostate [basal cells] salivary and lacrimal glands, Pathol Int 2007;57:245); widely expressed in other tissues
Negative staining: invasive ductal carcinoma (breast), prostate adenocarcinoma
References: OMIM 608859
Also called thrombopoietin receptor (TPO-R), myeloproliferative leukemia virus oncogene (MPL)
Binding to thrombopoietin induces megakaryocyte proliferation and differentiation and prevents apoptosis
Mutations present in some patients with congenital amegakaryocytic thrombocytopenia, characterized by severe congenital thrombocytopenia with no megakaryocytes in the bone marrow (Hum Mutat 2006;27:296)
MPL mutations in myelofibrosis patients are associated with more severe anemia (Br J Haematol 2007;137:244)
Thrombopoietin receptor agonists may be useful for treating thrombocytopenia (Blood 2007;109:4739)
Uses: differentiate essential thrombocythemia (variable but weak/negative staining) from reactive thrombocytosis (positive staining, Blood 2002;99:4131)
Positive staining (normal): hematopoietic stem cells and progenitor cells (J Transl Med 2006;4:9), megakaryocytes and progenitors, platelets
Diagrams: protein and site of various mutations
References: OMIM 159530, EntrezGene
Aka poliovirus receptor related 1 (PRR1), nectin1
Widely expressed adhesion molecule that is a component of the adherens junction; receptor for herpes simplex viruses 1 and 2
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes and erythroid lineage, epithelial cells, neurons, endothelium
Aka poliovirus receptor related 2 (PRR2)
Adhesion molecule that is a component of the adherens junction; receptor for herpes simplex virus
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes lineage, epithelial cells, neurons, endothelium
Also called nectin-3, poliovirus receptor-related protein 3 precursor
Aka granulocyte colony-stimulating factor receptor, G-CSFR
Specific regulator of myeloid proliferation and differentiation
Mutations present in some patients with severe congenital neutropenia
Positive staining (normal): granulocytes (all), monocytes, platelets, endothelium, placenta, trophoblastic cells
Positive staining (tumors): cultured tumor cells
Negative staining: eosinophils, lymphocytes, erythrocytes
Aka c-fms, receptor for macrophage colony stimulating factor, CSF-1R
Localized on cytoplasmic membrane; mediates biologic activity of CSF-1
v-fms is a viral oncogene present in the feline McDonough sarcoma virus (has several substitute mutations)
Related to platelet derived growth factor receptor, c-kit, vascular endothelial growth factor receptor, fibroblast growth factor receptor, high affinity nerve growth factor (TrkA)
Deficiency causes reduced osteoclasts and macrophages, abnormal bone remodeling and osteopetrosis, abnormal breast development and decreased fertility
Positive staining (normal): macrophages and precursors, osteoclasts, placental trophoblast, breast tissue, microglia, neurons, astrocytes
Positive staining (tumors): 10% AML, some endometrial, ovarian and breast cancers, vascular smooth muscle cells in atheromas, choriocarcinoma cells
GM-CSF receptor alpha chain
Primary binding subunit of GM-CSF receptor
Positive staining (normal): monocytes, neutrophils, eosinophils, fibroblasts, endothelial cells, dendritic cells
Summary: proto-oncogene activated in GIST tumors
Aka c-kit, stem cell factor receptor
Gene at 4q11-21
Receptor for kit protein, a 145 kD tyrosine kinase growth factor receptor protein important for development and survival of mast cells, hematopoietic stem cells, melanocytes, germ cells, interstitial cells of Cajal
Has activating or gain of function mutations in most GIST tumors, often at exon 11, less often at exons 9 and 13, Hum Path 2002;33:484
Tyrosine kinase activity of c-kit in GIST and bcl-abl overexpression in CML are inhibited by imatinib mesylate (Gleevec, STI571), a tyrosine kinase inhibitor used to treat these diseases, Hum Path 2002;33:466
Uses: confirming diagnosis of GIST (but see other CD117+ tumors below), possibly confirm chronic intestinal pseudo-obstruction, AJSP 2003;27:228
Interpretation: should be strong and diffuse cytoplasmic staining, like the positive control
Positive staining (normal): interstitial cells of Cajal, hematopoietic progenitor cells, melanocytes, embryonic/fetal brain, endothelium, gonads, mast cells, breast epithelium, germ cells
Positive staining (tumors): AML, angiomyolipoma (AJSP 2002;26:493), angiosarcomas (50%), clear cell sarcoma, CML, epithelioid sarcoma, Ewing sarcoma, gastrointestinal autonomic tumors, gastrointestinal stromal tumors (GIST), granulocytic sarcoma, Hodgkin’s lymphoma (some Reed-Sternberg cells), intraabdominal fibromatosis (depends on antibody used, AJSP 2001;25:549), mast cell disease (also positive for tryptase, CD43, CD68); melanoma, mesenteric fibromatosis (variable, AJSP 2002;26:1296), metanephric adenosarcoma (AJSP 2001;25:1451), omental mesenchymal tumor, osteosarcoma, rhabdomyosarcoma, sclerosing mesenteritis (variable), seminomas /dysgerminomas, small cell lung cancer (Hum Path 2002;33:1182), synovial sarcoma (~10%, usually cytoplasmic staining), adenoid cystic carcinoma of salivary gland (strong staining)
Negative staining: alveolar soft part sarcomas, desmoplastic small round cell tumors, glomus tumors, leiomyomas (retroperitoneal, colorectal), leiomyosarcomas, myxomas (cardiac), schwannomas (colorectal), smooth muscle tumors of uncertain malignant potential, solitary fibrous tumors
Micro images: GIST vs. solitary fibrous tumor; malignant stromal tumor of gallbladder (figure 4); GIST (figures G, H); interstitial cells of Cajal in patient with multiple GIST tumors
References: Archives 2002;126:1189, AJSP 2002;26:486
Reserved for interferon alpha / gamma receptor
Interferon gamma receptor
Positive staining (normal): macrophages, B cells
Aka TNFR1, receptor for tumor necrosis factor alpha and beta, type I
Receptor binding to ligand causes apoptosis
CD120b
Aka receptor for tumor necrosis factor (TNF) alpha and beta, type II
Aka Interleukin 1 receptor (IL-1R) type I, IL1-alpha
Interleukin-1, an inflammatory mediator, consists of 2 separate but related proteins, IL1-alpha and IL1-beta
Positive staining (normal): T cells, thymocytes, fibroblasts, endothelial cells
CDw121b
Aka Interleukin 1 receptor (IL-1 R) type II, IL1-beta
May inhibit IL1 activity by acting as a decoy target for IL1
Positive staining (normal): B cells, macrophages
Aka Interleukin 2 receptor beta chain (IL-2R beta)
Critical component of IL-2 and IL-15-mediated signaling
Positive staining (normal): NK cells, B cells, T cells, monocytes
Aka Interleukin 3 receptor alpha subunit
Associates with the GM-CSF receptor (GMR beta)
Positive staining (normal): plasmacytoid monocytes (bright with flow cytometry, AJSP 2002;26:852)
Aka Interleukin 4 receptor
Receptor subunit for Interleukin-4 and 13
Positive staining (normal): mature B cells, T cells; hematopoietic precursors; fibroblasts, endothelial cells
Aka Interleukin 5 receptor alpha subunit
Therapeutic target of eosinophilic inflammation involved in bronchial asthma
Positive staining (normal): eosinophils, activated B cells, basophils
Aka Interleukin 6 receptor
Continuous expression of IL-6 and CD130, ligands for CD126, causes hypergammaglobulinemia, glomeruloproliferative nephritis and lymphoid infiltration in some organs
Dysregulated stimulation may cause myeloma and plasmacytoma
Positive staining (normal): T cells, monocytes, activated B cells, hepatocytes
Aka Interleukin 7 receptor
Positive staining (normal): B cell precursors, most T cells, monocytes
See CD181
Reserved for Interleukin 9 receptor
Aka gp 130
Required for transducing biological activities of interleukin-6, interleukin-11, leukemia inhibitory factor, ciliary neurotrophic factor, oncostatin M, and cardiotrophin-1
In human, IL-6 and oncostatin M dependent activation of gp130 are involved in multiple myeloma
Positive staining (normal): almost all cell types (low levels)
Aka common beta subunit
Does not bind any cytokine by itself, but is a component of the high affinity IL-3, GM-CSF and IL-5 receptors
Defective CDw131 is associated with protein alveolar proteinosis
Positive staining (normal): myeloid (early and mature), early B cells
Aka common cytokine receptor gamma chain - receptor for IL-2, IL-4, IL-7, IL-9 and IL-15
Mutation in humans causes X-linked severe combined immunodeficiency (no T cells, no NK cells)
CD132 is a target molecule for gene therapy for X-SCID
Positive staining (normal): T cells, B cells, NK cells, monocytes/macrophages, neutrophils
Aka tax-transcriptionally activated glycoprotein 1 receptor, OX40 antigen, lymphoid activation antigen
Aka macrophage stimulating protein receptor, msp receptor
May regulate ciliary beat frequency in epithelial cells
Positive staining (normal): skin, kidney, lung, liver, intestine, and colon
Costimulator of T cell proliferation
Positive staining (normal): T cells, especially CD45RA and CD45R0; also B cells, monocytes, epithelial cells
Aka heparan sulfate proteoglycan, syndecan-1
Mediates cell adhesion, growth factors; associated with late stage of B cell differentiation
Integral membrane protein is a receptor for extracellular matrix
Loss of CD138 expression is associated with tumor aggressiveness in squamous cell carcinoma (SCC) of head and neck and larynx; levels also reduced in invasive SCC but not in SCC-in situ
Interpretation: membranous staining
Positive staining (normal): B cell precursors, plasma cells, stratified squamous epithelium
Positive staining (tumors): keratoacanthoma, myeloma, plasmablastic lymphoma (strong), primary effusion lymphoma, pyothorax associated lymphoma
Negative staining: mature B cells, other lymphomas (even plasmacytoid lymphomas)
Micro images: keratoacanthoma #1 (figure B); #2 (figure B); invasive squamous cell carcinoma
References: Mod Path 2002;15:45; AJSP 2002;26:1363
Positive staining (normal): B cells, monocytes, granulocytes, erythrocytes (weak), dendritic cells, glomeruli
Negative staining: T cells
Aka alpha platelet derived growth factor receptor
CD140b
Aka beta platelet derived growth factor receptor
Aka thrombomodulin
75kD transmembrane glycoprotein and cofactor for the thrombin-mediated activation of protein C
Marker of mesotheliomas, endothelial cells and coagulation factor
Important fibrinolytic inhibitor, as it decreases the activation of plasminogen to plasmin
Critical for activation of protein C and initiation of the protein C anticoagulant pathway
Plasma CD141 levels are associated with endothelial damage
Interpretation: membranous staining pattern, often focal (cytoplasmic staining may be artifactual)
Uses:
Mesothelioma vs. lung adenocarcinoma: 64% sensitive, 95% specific for mesotheliomas, but must exclude vasculature; often membranous staining of periphery with isolated papilla; negative staining in sarcomatoid mesotheliomas; considered to have a “secondary” role as other markers are better, Hum Path 2002;33:953
Urothelial carcinomas (positive) vs. renal cell, prostate, endometrial or colonic carcinomas, AJSP 2001;25:1380
Squamous cell carcinomas (positive), AJCP 1998;110:385, AJSP 2003;27:150
Positive staining (normal): endothelial cells, megakaryocytes, keratinocytes, mesothelial cells, monocytes, neutrophils, platelets, smooth muscle cells, syncytiotrophoblasts, synovial lining cells, urothelium
Positive staining (tumors): mesothelioma (epithelioid), squamous cell carcinomas, trophoblastic tumors, urothelial carcinomas, vascular tumors (including angiosarcoma), synovial sarcoma (diffusely positive in 10%, AJSP 2001;25:610)
Negative staining: adenocarcinoma of colon, endometrium, kidney, lung (usually), prostate; sarcomatoid mesothelioma,
Aka coagulation Factor III, thromboplastin, tissue factor
Major initiator of clotting in normal hemostasis and many thrombotic diseases, via complex with factor VIIa
Also binds zymogen factor VII, the inactive precursor form; once bound, a variety of serine proteases rapidly activate factor VII to VIIa via limited proteolysis
Normally absent from all cells in direct contact with plasma
Positive staining (normal): epidermal keratinocytes, glomerular epithelial cells and various other epithelia, adventitial cells of blood vessels, astrocytes, myocardium, Schwann cells, stromal cells of liver, pancreas, spleen and thyroid
Aka angiotensin-converting enzyme, ACE, peptidyl dipeptidase A
Involved in metabolism of angiotensin II and bradykinin; also cleaves substance P and LH-RH
Patients with high activity have DD genotype, associated with MI, strokes, diabetic nephropathy
Necessary for spermatozoa to bind to egg and associated with better penetration of egg
Positive staining (normal): endothelial cells of small/medium arteries, lung capillary endothelium, proximal renal tubule brush borders, basal ganglia neuropil, granulosa cells, Leydig cells, variable on other cells
Endothelial-specific cadherin localized at intercellular junctions
Aka vascular endothelial-cadherin precursor, VE-cadherin, cadherin 5
Cadherins are cell adhesion proteins that preferentially interact with themselves in a homophilic manner in connecting cells, thus contributing to the sorting of heterogeneous cell types
Positive staining (normal): endothelial cells, brain
Aka melanoma cell adhesion molecule (MEL-CAM), cell surface glycoprotein MUC18
May be a neural crest cell adhesion molecule during embryogenesis
Associated with tumor progression and the development of metastasis in human malignant melanoma
Sensitive but nonspecific marker of desmoplastic/spindle cell melanoma; use if suggestive histology, S100 positive, melanoma markers otherwise negative, AJSP 2001;25:58
Interpretation: expression is membranous
Positive staining (normal): vascular smooth muscle, endothelium, intermediate trophoblast in exaggerated placental sites and placental site trophoblastic tumors (Hum Path 1999;30:687), subpopulation of T cells, endothelium, smooth muscle, Schwann cells
Positive staining (tumors): clear cell sarcoma (90%), leiomyosarcomas (almost all), melanoma (desmoplastic-84%, epithelioid melanomas-100%, advanced primary tumors and metastatic tumors), melanotic schwannoma (100%), MPNST (27%), neurofibroma (40%), prostatic adenocarcinoma and high grade PIN, squamous cell carcinomas (some), vascular sarcomas (almost all)
Negative staining: normal melanocytes, melanocytic nevi, cellular blue nevus, thin primary melanomas, placental site nodules (or focal), epithelioid trophoblastic tumors (or focal), cytotrophoblast, atypical fibroxanthoma
Reference: AJSP 2001;25:58
Aka neurothelin, extracellular matrix metalloproteinase inducer
Positive staining (normal): all leukocytes, red blood cells, platelets and endothelial cells
Aka HPTP-eta
May be involved in contact inhibition of cell growth
Positive staining (normal): granulocytes, monocytes, memory T cells, dendritic cells, platelets, fibroblasts, neurons, Kupffer cells
Deleted (now designated CD47R) at the 7th HLDA Workshop
Reference: Tissue Antigens 2000;56:258
Aka signal lymphocyte activation molecule (SLAM)
Costimulatory molecule on B lymphocytes and dendritic cells
Positive staining (normal): thymocytes, CD45RO positive subpopulation of T cells, B cells, dendritic cells, endothelium
May modify integrin function or signaling
Positive staining (normal): endothelium, platelets, megakaryocytes, epithelium
Aka cytotoxic T lymphocyte-associated protein-4, CTLA4
Negative regulator of T cell activation
CTLA4 restriction fragment length polymorphisms are linked to various autoimmune disorders
Shares sequence homology with CD28; also shares ligands CD80 and CD86 with CD28
Positive staining (normal): activated but not resting T cells, activated B cells
References: 123890
Aka CD30 ligand
Enhances CD3-activated T lymphocyte proliferation
Aka CD40 ligand, CD40L, TNF-related activation protein (TRAP)
Regulates B cell function by engaging CD40
Defective gene prevents immunoglobulin class switch and is associated with hyper IgM syndrome, autoimmune hematologic disorders, disorganized nodal follicular architecture and PAS-positive plasmacytoid cells containing IgM, lymph nodes without germinal centers, shortened lifespan, often with gastrointestinal cancers (cholangiocarcinoma, hepatocellular carcinoma, and adenocarcinoma) and Cryptosporidium parvum infection
Positive staining (normal): T cells
Aka polio virus receptor
Involved in intercellular adhesion
Positive staining (normal): embryonic structures giving rise to spinal cord anterior horn motor neurons
Aka ADAM8
May play a role in muscle differentiation
Possible role in neutrophilic extravasation
Positive staining (normal): neutrophils, monocytes
CD156b
Aka Tumor necrosis factor Alpha Converting Enzyme (TACE), ADAM17
Adhesion structure; releases soluble forms of tumor necrosis factor and transforming growth factor-alpha from cells
Positive staining (normal): all cells examined, with pro-domain removed
Aka Bone marrow STromal cell antigen 1 (BST1)
Facilitates pre-B-cell growth
33% homology to CD38
Overexpression may cause polyclonal B-cell abnormalities in rheumatoid arthritis
Positive staining (normal): granulocytes, monocytes, B cell progenitors, T cell subpopulations
Member of KIR (killer cell immunoglobulin like receptor) family, also called killer cell inhibitory receptors
Binding by HLA class I molecules causes inhibition of NK or T cell cytotoxic activity
Melanoma specific cytotoxic T lymphocytes may express KIR and regulate their ability to kill these tumors
Positive staining (normal): Natural killer cells (NK cells), some T cells
CD158a
Aka KIR2DL1/p58.1
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset
CD158b
CD158b1 aka KIR2DL2/p58.2
CD158b2 aka KIR2DL3/p58.3
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset, rare T cells
CD158c-KIR2DS6/KIRX
CD158d-KIR2DL4
CD158e1-KIR3DL1/p70
CD158e2-KIR3DS1/p70
CD158f-KIR2DL5
CD158g-KIR2DS5
CD158h-KIR2DS1/p50.1
CD158i-KIR2DS4/p50.3
CD158j-KIR2DS2/p50.2
CD158k-KIR3DL2/p140
CD158z-KIR3DL7/KIRC1
Aka NKG2A, killer cell lectin-like receptor subfamily C member 1
Mediates signaling in the killing process by NK cells
Positive staining (normal): NK cells
Aka BY55
Expression tightly associated with peripheral blood NK cells and CD8+ T lymphocytes with cytolytic effector activity
Positive staining (normal): circulating NK (CD56 dim, CD116+) and T cells, spleen, small intestinal intraepithelial lymphocytes
Aka killer cell lectin-like receptor subfamily B, member 1
May mediate NK cell function
Positive staining (normal): NK cells, subset of CD4+ and CD8+ T cells, memory T cells, thymocytes (some)
Aka P-Selectin Glycoprotein Ligand 1, PSGL-1
Important in adhesive interactions between circulating leukocytes and platelets and endothelial cells
Mediates rolling on activated endothelium or activated platelets (which express P selectin / CD62P) and other leukocytes at inflammatory sites
Site of binding of human granulocyte ehrlichiosis bacteria
Positive staining (normal): myeloid cells, stimulated T cells
CD162R
Positive staining (normal): NK cells
Hemoglobin/haptoglobin scavenger receptor
Soluble form attenuates immune response
Positive staining (normal): monocytes/macrophages
Positive staining (disease): histiocytic sarcoma (Diagn Pathol 2007;2:7)
Micro images courtesy of Drs. Charles J. Sailey, Borislav A. Alexiev and John C. Papadimitriou, Maryland (USA): histiocytic sarcoma
Aka MUC-24, sialomucin
Mucin-like cell surface glycoprotein that facilitates adhesion of CD34+ cells; regulates hematopoietic cell proliferation
Positive staining (normal): small and large bowel epithelia; lung, thyroid epithelia
Positive staining (tumors): colorectal carcinoma, pancreatic adenocarcinoma
Involved in adhesion between thymocytes and thymic epithelial cells
Positive staining (normal): immature thymocytes, monocytes, platelets, CNS neurons, islet cells, Bowman’s capsule of kidney
Positive staining (tumors): many T-acute lymphoblastic leukemias (ALL)
Aka Activated Leukocyte Cell Adhesion Molecule (ALCAM)
Adhesion molecule, binds to CD6
Involved in neuronal neurite extension, embryonic hemopoiesis, embryonic angiogenesis
Positive staining (normal): neurons, activated T cells, activated monocytes, epithelium, fibroblasts
Aka Discoidin Domain Receptor 1, DDR1
Has homologous region to the Dicytostelium discoideum protein discoidin I in extracellular domain
Tyrosine kinase receptor, may be important in cytoskeletal organization and the ability to align with other cells during aggregation
Receptor tyrosine kinases help cells communicate with their microenvironment and regulate cell growth, differentiation and metabolism.
Activated by collagen types I-V, VIII
May have a role in tumor invasion and metastasis
Positive staining (normal): epithelial cells (breast, kidney, lung, GI, brain)
Positive staining (tumors): carcinomas (various)
Aka Receptor for Hyaluronic Acid-Mediated Motility (RHAMM)
Binding to hyaluron stimulates ciliary beating
Also has role in cell signaling, migration and adhesion
Positive staining (normal): bronchial epithelium, CNS neurons
Aka sialoadhesin
Macrophage-restricted cellular interaction molecule that binds sialylated ligands
Highly expressed on macrophages in chronically inflamed tissues, such as rheumatoid synovium and atherosclerotic plaques
Positive staining (normal): macrophages (all sites but microglia)
Negative staining: microglia
Aka Sialic acid binding IG-like LECtin 5 (SIGLEC5)
May function in cell-cell interaction
Positive staining (normal): neutrophils
Aka L1
Adhesion molecule required for normal neurohistogenesis
Mutations cause CRASH (Corpus callosum hypoplasia/agenesis, Retardation, Aphasia, Spastic paraplegia/shuffling gait and Hydrocephalus due to stenosis of aqueduct of Sylvius), an X linked neurologic disorder
May mediate kidney branching morphogenesis, maintenance of lymph node architecture during immune response, co-stimulation of T-cell activation in vitro
Positive staining (normal): post-mitotic neurons, glia, epithelial cells (some), lymphoid cells (some), myeloid (some), monocytes
Aka SIRP alpha
Adhesion structure
Aka blood group H2
Marker of early hematopoiesis
Positive staining (normal): CD34+ hematopoietic progenitor cells
Negative staining: mature lymphocytes
Aka Lewis Y antigen
Marker of early hematopoiesis
Positive staining (normal): CD34+ hematopoietic progenitor cells
Negative staining: mature lymphocytes
Aka Tn
Simple mucin-type carbohydrate antigen produced in the initial steps of mucin biosynthetic pathway, due to aberrant or incomplete glycosylation of mucins
CD175s
Aka Sialyl Tn (STN)
Carbohydrate associated with apomucins MUC1, MUC2; produced in the initial steps of mucin biosynthetic pathway
Presence associated with aggressive tumors
High pre-operative serum levels predict liver metastasis and poor prognosis after resection for gastric cancer
Definitive Phase III trial of STN vaccine in metastatic breast cancer patients began 2001
Positive staining (tumors): carcinomas
Aka Thomsen-Friedenreich (TF) oncofetal blood group antigen, galactose beta 1-3 N-acetylgalactosamine alpha
Occurs in colon cancer and colitis
Aka NB1 glycoprotein
Major immunogenic molecule of neutrophil membrane
Positive staining (normal): myeloid cells
Aka CD95 ligand, Fas ligand (FasL)
Important role in T cell mediated cytotoxicity; induces apoptosis in Fas-expressing target cells
Cells in immune privileged sites (testis, anterior chamber of eye, placenta) constitutively express FasL, which induces apoptosis in Fas-expressing infiltrating T cells, minimizing inflammatory responses that might damage important physiologic functions at these sites
May influence interaction of tumor cells with host immune system; theory is that FasL+ tumor cells induce apoptosis in infiltrating Fas+ mononuclear cells
Fas-FasL binding triggers apoptosis in lymphocytes
Mutations may be related to some cases of Systemic Lupus Erythematosis (SLE)
Processed by metalloproteases which cause shedding of extracellular portion into blood (sFas L)
Positive staining (normal): activated and cytotoxic T cells, testis, anterior chamber of eye, placenta; also Sertoli cells, neurons, thyroid epithelial cells
Positive staining (tumors): Reed-Sternberg cells of Hodgkin’s lymphoma (nodular sclerosis and mixed cellularity, AJSP 2001;25:388)
Aka VpreB1
Associates non-covalently with CD179b to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Positive staining (normal): preB cells
CD179b
Aka lambda-5
Associates non-covalently with CD179a to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Mutations impair B cell development and cause agammaglobulinemia
Positive staining (normal): preB cells
Aka RP105
Regulates B cell recognition of lipopolysaccharide, a membrane constituent of gram-negative bacteria
Positive staining (normal): mantle zone and marginal zone B cells (strong), other B cells (weak/negative); peripheral blood monocytes, dendritic cells
Also called CXCR1, IL8Ralpha; previously called CDw128A
Chemokine receptor, powerful neutrophil chemotactic factor
Positive staining (normal): neutrophils, basophils, T cell subset, monocytes, keratinocytes
Positive staining (disease): T cells in allergic rhinitis (J Immunol 2004;172:268)
Aka CXCR3
Receptor for some chemokines; binding of chemokines to CD183 induces integrin activation, cytoskeletal changes and chemotactic migration in inflammation-associated effector T cells
CD183+ T cells detected in inflamed tissues of patients with juvenile rheumatoid arthritis, multiple sclerosis, sarcoidosis, hepatitis C
Positive staining (normal): T cells in inflamed tissue, eosinophils, plasmacytoid dendritic cells, hematopoietic progenitors
Negative staining: naïve T cells in peripheral blood
Aka CXCR4, Stromal cell Derived Factor 1 (SDF1)
Receptor for the CXC chemokine SDF-1
Also major HIV/SIV co-receptor (with CCR5/CD195)
Involved in B cell development, myelopoiesis, cardiac ventricular septum formation, blood vessel formation in GI tract, cerebellar granular cell development
Positive staining (normal): all mature blood cells, blood progenitor cells, endothelial and epithelial cells, astrocytes, neurons
No information available
No information available
Aka CCR5
Macrophage surface receptor and attachment site for HIV and SIV, with CXCR4 (CD184); works with CD4
Receptor for CD8 chemokines RANTES, MIP 1-alpha and MIP 1-beta.
No information available
Aka OX2
An immunoadhesin that may deliver immunosuppressive signals and regulate autoimmune disorders
Inhibitory for macrophage lineage cells
Positive staining (normal): follicular dendritic cells, thymocytes, B cells, T cells, neurons, kidney glomeruli, syncytiotrophoblast, endothelial cells
Binds protein C in a calcium-dependent manner
Aka Endothelial Protein C Receptor (EPC R), protein C receptor
Protein C is a vitamin K dependent enzyme with major role in coagulation of blood; activated when thrombin binds to thrombomodulin on endothelium.
Mutations in CD201 and thrombomodulin associated with late fetal loss; similar mutation associated with venous thromboembolism and myocardial infarction
Positive staining (normal): endothelial cells (not in liver and kidney)
Aka Tie2 (Tyrosine kinase with Ig-like loops and Epidermal growth factor homology domains), aka Tek
Receptor tyrosine kinase at #9p21, binds to angiopoietin-1
May be earliest mammalian endothelial cell lineage marker
Involved in vein morphogenesis and communication between endothelial and smooth muscle cells for remodeling and repair of blood vessels
Defects associated with inherited venous malformations
Positive staining (normal): endothelial cells, hematopoietic cells
Aka E-NPP3/PDNP3
Enzyme that catalyzes hydrolysis of oligonucleotides, nucleoside phosphates, and NAD
Positive staining (normal): prostate, uterus, basophils, mast cells, gliomas, myeloid cells
Aka macrophage scavenger receptor 1
Plays a role in endocytosis of macromolecules
Positive staining (normal): myeloid cells
Aka DEC205
Possible antigen-uptake receptor with a role in initiating immune response
Positive staining (normal): dendritic cells
Aka macrophage mannose receptor
Acts in phagocytosis and pinocytosis of mannose-containing solutes
Positive staining (normal): dendritic cells
Aka langerin (Langerhans cell specific c-type lectin)
Functions as endocytic receptor
Localized to Birbeck granules
Mannose binding to this protein may cause antigen internalization into Birbeck granules and access to a nonclassical antigen-processing pathway
Positive staining (normal): Langerhans cells (immature dendritic cells of epidermis and mucosa)
Dendritic cell LAMP (DC-Lamp)
Indicates dendritic cell maturation
Positive staining (normal): dendritic cells
Aka DC-Sign
Binds to HIV1 gp120
Mediates transient adhesion of dendritic cells with T cells
Positive staining (normal): dendritic cells
Aka IL-10 receptor
Interleukin-10 (124092) produced by B cells, T helper cells, and monocyte/macrophages, exhibits diverse activities on different cell lines
IL10 inhibits macrophage activation by interferon-gamma
Positive staining (normal): monocytes, B and T cells, large granular lymphocytes, spleen, thymus, placenta, lung, liver
Aka IL-12 receptor
Interleukin-12 promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell responses and interferon-gamma production.
Lack of IL12 associated with severe, idiopathic mycobacterial and Salmonella infections, mature granulomas
Positive staining (normal): T cells, NK cells
Aka IL-13 receptor, alpha 1
Binds IL-13 with low affinity
With IL-4r-alpha, can form a functional receptor for IL-13
Positive staining (normal): ubiquitous, B-cells, T-cells and endothelial cells, highest levels in heart, liver, skeletal muscle and ovary
CD213a2
Aka IL-13 receptor, alpha 2
Inhibits binding of interleukin-13 to the IL13 cell surface receptor
Positive staining (normal): placenta
No information available
Aka IL 17 receptor
Cytokine that is induced in activated CD4+ T cells
IL17 induces stromal cells to produce proinflammatory and hematopoietic cytokines; enhances expression in fibroblasts of ICAM-1
No information available
Aka insulin receptor
Aka insulin-like growth factor 1 receptor
Mediates insulin stimulated DNA synthesis and IGF1 stimulated cell proliferation and differentiation
Often overexpressed in malignant tissue, where it functions as an anti-apoptotic agent by enhancing cell survival
Aka insulin-like growth factor 2 receptor, mannose 6 phosphate receptor
Also a receptor for lysosomal hydrolases (i.e. assists in sorting lysosomal enzymes from Golgi apparatus or extracellular space to lysosomes)
Aka Lymphocyte-Activation Gene 3 (LAG-3)
Homologous to CD4
Associates with MHC class II molecules on monocytes/dendritic cells, which are subsequently activated
May help activated CD4+ and CD8+ T cells to fully activate monocytes and dendritic cells, leading to optimized MHC class I and class II T cell responses
Positive staining (normal): activated T cells, activated NK cells
Aka gamma-glutamyltransferase
Gene at 22q11.1-q11.2
Catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors, which maintains a homeostatic balance regarding oxidative stress.
Aka Leu13, interferon-inducible transmembrane protein 1
Involved in relaying antiproliferative and homotypic adhesion signals
Aka DNAM-1, Platelet and T cell Activation antigen 1 (PTA1)
Mediates adhesion to an unknown ligand
T cell expression increased in some patients with autoimmune disease and viral infection
Positive staining (normal): NK cells, platelets, monocytes, subset of B and T cells
Negative staining: granulocytes, erythrocytes
Aka melanotransferrin
Cell-surface glycoprotein found on melanoma cells, with sequence similarity and iron-binding properties of transferrin superfamily
Aka Lymphocyte antigen 9
May be involved in adhesion between T cells and accessory cells
Aka prion protein (“PRotein INfectious agent”)
Mutations associated with Gerstmann-Straussler disease, Creutzfeldt-Jakob disease (CJD), familial fatal insomnia, which are neurodegenerative conditions transmissible by inoculation or inherited as autosomal dominant disorders
Aberrant isoforms can act as an infectious agent in these disorders as well as in kuru and in scrapie in sheep
Replication (infectivity) occurs as abnormal protein with conformational change recruits cellular prion and converts it into infective form with same conformational change
Positive staining (normal): neurons (nonpathogenic isoform)
Reference: 176640
Aka T cell Acute Lymphoblastic Leukemia Antigen-1 (TALLA-1), TM4SF2, A15
Involved in X-linked mental retardation, Nat Genet 2000;24:167
Positive staining (normal): brain neurons
Positive staining (tumors): T cell acute lymphoblastic leukemia, neuroblastoma cells
Negative staining: B cells, monocytes
CD232
Aka Virus Encoded Semaphoring Protein Receptor (VESP R)
May function as an immune modulator during virus infection.
Aka band 3
Erythrocyte membrane protein that functions as an anion (chloride/bicarbonate) exchanger and attachment site for cytoskeleton (where spectrin/actin bind to membrane lipid bilayer)
Truncated form of CD233 is expressed in kidney and involved in acid secretion
Mutations cause hereditary spherocytosis or distal renal tubular acidosis (due to defective acid secretion)
Other mutations cause novel blood group antigens which form the Diego blood group system
Southeast Asian ovalocytosis is due to heterozygous deletions, common where Plasmodium falciparum malaria is endemic, associated with abnormally rigid, stomatocytic erythrocytes, asymptomatic; children are protected against cerebral malaria
Positive staining (normal): erythrocyte plasma membrane (strong), basolateral membrane of a-intercalated cells of the distal tubules and collecting ducts of the kidney
Negative staining: all other cells
Aka Duffy blood group antigen (Fy glycoprotein); erythrocyte chemokine receptor, Duffy Antigen Receptor for Chemokines (DARC)
RBC receptor for Plasmodium vivax, a malarial parasite
Negativity associated with sickle cell trait, due to common protection against malaria provided by both traits African-Americans often Duffy negative and resistant to P. vivax malaria
Positive staining (normal): endothelial cells of post-capillary venules, Purkinje cells of cerebellum
Aka Glycophorin A
Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells
CD235b
Aka Glycophorin B
Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells
CD235ab
Aka Glycophorin A/B crossreactive antibodies
Positive staining (normal): erythroid cells
Aka Glycophorin C/D
Positive staining (normal): erythroid cells
CD236 R
Aka Glycophorin CRegulates mechanical stability of red cells
Mutations cause Gerbich and Yus blood group phenotypes
Positive staining (normal): erythroid cells
Aka Kell blood group antigen
Positive staining (normal): erythroid cells
Aka Lutheran blood group antigen; B-CAM
May mediate cell-cell, cell-matrix adhesion, signal transduction
Positive staining (normal): erythroid cells
Also called RH 30 CE, Rh blood group Cc and Ee blood group antigens; encodes RhC and RhE antigens on a single polypeptide
On #1p36.11 adjacent to RH D gene
Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations
Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein; Rh proteins form a core complex critical to structure of erythrocyte membrane (Blood Rev 2006;20:93); may play a role in ammonia transport (J Biol Chem 2002;277:12499, but see Transfus Clin Biol 2006;13:132)
Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)
Rarely causes hemolytic disease of newborn (Transfus Med 2000;10:305)
Uses: blood typing
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, Blood 2000;95:375, OMIM 111700
CD240 D
Also called RH30 D, Rh blood group D blood group antigen; is major antigen of the Rh system
On #1p36.11 adjacent to RHCE gene
Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations
Weak D, formerly called D(u), occurs in 0.2 to 1% of whites; exhibits reduced expression of D antigen (Blood 1999;93:385); should not be labeled as Rh negative (Curr Opin Hematol 2006;13:476)
Individuals are classified as Rh positive or negative based on presence or absence of highly immunogenic D antigen on red cell surface
May have arisen historically by duplication of RHCE gene (Blood 2002;99:2272)
Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)
Hemolytic disease of fetus and newborn: usually due to Rh negative woman whose partner is Rh+ or heterozygous and fetus is Rh+; woman has preexisting anti-RhD antibodies that cross placenta and harm fetus (Immunohematol 2006;22:188)
Can use maternal plasma in alloimmunized pregnancies to determine fetal RhD status (Fetal Diagn Ther 2006;21:404), or for RHD and RHCE genotyping (Prenat Diagn 2005;25:1079); genotyping from amniotic fluid or chorionic villi sampling was performed in past, but is more invasive (N Engl J Med 1998;339:1734, Clin Exp Med 2002;2:77)
Rh positive mothers may rarely (0.15%) develop new antibodies (other than anti-RHD) in third trimester, but no clinical significance (J Matern Fetal Neonatal Med 2007;20:59)
Having Rh negative mother may be risk factor for autistic children, due to use of mercury containing Rho-immune globulin (J Matern Fetal Neonatal Med 2007;20:385)
Uses: blood typing
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, OMIM 111680, Wikipedia, eMedicine (Rh incompatibility)
CD240 DCE
Rh30D/CE crossreactive monoclonal antibodies
Uses: blood typing
Positive staining (normal): erythroid cells of normal Rh types
Negative staining: Rh null erythrocytes
References: Washington State University
Also called RH50 glycoprotein, RHAG, Rhesus blood group associated glycoprotein
Located at #6p21.1-p11
Is a strictly required posttranscriptional factor regulating Rh membrane expression (Blood 2002;100:1038)
Also appears to be an ammonium transporter (Proc Natl Acad Sci USA 2004;101:17222) and a CO2 channel (FASEB J 2007 Aug 21; [Epub ahead of print])
Defects cause Rh-null phenotype (OMIM 268150), associated with a chronic hemolytic anemia and spherostomatocytosis (J Biol Chem 1998;273:2207)
Uses: blood typing
Positive staining (normal): erythroid cells
References: OMIM 180297
Also called intercellular adhesion molecule 4 (ICAM-4), Landsteiner-Wiener (LW) blood group protein
Discovered with antibody raised in guinea pigs injected with the cells of rhesus monkeys, but Rh designation had already been taken
Binds to CD11a/CD18, CD11b/CD18 and CD11c/CD18 (Blood 2007;109:802)
May be critical in erythroblastic island formation, where erythroid progenitors differentiate (Blood 2006;108:2064)
May be ligand for platelet-activated alpha IIb beta 3 integrin (J Biol Chem 2003;278:4892)
In sickle cell disease, contributes to red cell-endothelial cell adhesion and vasoocclusion (Transfus Clin Biol 2006;13:44)
Uses: no significant clinical use by pathologists
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, OMIM 111250
Click
Also called Natural Killer cell receptor 2B4
Regulates NK and T cell function in multiple ways (J Immunol 2005;175:2045)
Coexpression of 2B4 and CD160 defines a CD8+ T lymphocyte subpopulation with high cytolytic effector activity (Eur J Immunol 2006;36:2359)
Binds to CD48 (J Immunol 2006;176:4646), and CD244-CD48 interactions prevent NK cells from killing each other (Blood 2007;110:2020)
Functional changes are associated with X linked lymphoproliferative disease (J Exp Med 2000;192:337, J Immunol 2000;165:2932)
Diagrams: NK cell receptors
Uses: no significant clinical use by pathologists
Positive staining (normal): NK cells, CD8+ T cells, monocytes and basophils (Eur J Immunol 1999;29:1676), eosinophils (J Immunol 2005;174:110), spleen (Tissue Antigens 1999;54:27)
References: OMIM 605554
Also called p220/240
Very little information is available for CD245 directly; appears to be identical to NPAT (nuclear protein, ataxia-telangiectasia locus)
NPAT links S phase cyclin E/Cdk2 kinase activity to replication-dependent histone gene transcription (Biochemistry 2006;45:15915, Mol Cell Biol 2005;25:6140)
Uses: no significant clinical use by pathologists
Positive staining (normal): T cells (some), other white blood cells with varying intensity (Washington State Univ)
Also called ALK or ALK-1
Anaplastic lymphoma kinase gene at 2p23
Is NOT the same as Ki-1/CD30, as indicated by some references
Membrane spanning tyrosine kinase receptor; ligand is growth factor pleiotrophin
Normally expressed in developing nervous system and weakly in adult nervous system
In anaplastic large cell lymphoma, is usually fused with NPM (nucleophosmin) gene via t(2;5)(p23;q35), but also variants (Genes Chromosomes Cancer 2002;34:354)
ALK negative cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Path 2005;18:235), consensus criteria for diagnosis are lacking (AJCP 2007;127:707)
ALK mutation causes hereditary hemorrhagic telangiectasia type 2 (J Dent Res 2006;85:705)
Prognostic significance: ALK+ tumors have favorable prognostic significance in anaplastic large cell lymphomas [ALCL] (Blood 1999;93:3913), including primary CNS ALCL (AJSP 2003;27:487) and inflammatory myofibroblastic tumors (AJSP 2007;31:509)
Interpretation: usually cytoplasmic and nuclear staining
Uses: prognostic value in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor (see above), differentiate inflammatory myofibroblastic tumor (ALK+) from ALK negative spindled neoplasms in soft tissue (AJSP 2001;25:1364) and bladder (Mod Path 2007;20:592)
Positive staining (normal): embryonic neurons of CNS/PNS; weakly positive in adult brain
Positive staining (tumors): T/null cell anaplastic lymphomas (most), inflammatory myofibroblastic tumor (AJSP 2001;25:1364, AJSP 2001;25:761); diffuse large B cell lymphoma (rarely, Mod Path 2007;20:310); low level expression in some rhabdomyosarcomas, lipogenic tumors, Ewing’s/PNET, MFH, leiomyosarcoma and other soft tissue tumors (Hum Path 2004;35:711)
Negative staining: fibromatosis, GIST, nodular fasciitis, normal lymphoid tissue
Micro images: alveolar rhabdomyosarcoma (dot-like cytoplasmic staining-fig B); anaplastic lymphoma (fig C); anaplastic lymphoma-various images #1; #2; #3 (quality control); diffuse large B cell lymphoma (fig B); inflammatory myofibroblastic tumor #1 of bladder (fig d); #2 of abdomen (fig 2A); #3 of larynx (fig 2c); #4-site unspecified (fig B); #5-site unspecified (fig A); neuroblastoma (weak)
References: OMIM 105590
Also called T cell receptor zeta chain
Forms T cell-CD3 receptor complex with TCR alpha/beta and gamma/delta heterodimers and CD3-gamma, delta and epsilon (Proc Natl Acad Sci USA 1988;85:9709)
Couples antigen recognition to several intracellular signal transduction pathways; low expression causes impaired immune response
Low expression in tumor infiltrating T cells in various disorders - cancer of kidney (Cancer Invest 2004;22:871) and stomach (Cancer 2002;94:1437), Hodgkin’s lymphoma (Blood 1996;88:236); also active tuberculosis (J Infect Dis 2006;194:1385), systemic lupus erythematosus (J Immunol 2002;169:6048, Adv Med Sci 2006;51:181), normal pregnancy but not preeclampsia (Am J Obstet Gynecol 2003;189:843)
Defects cause primary T-cell immunodeficiency (OMIM 610163)
Diagrams: T cell activation
Uses: no significant clinical use by pathologists
Positive staining (normal): T cells
Micro images: gastric carcinoma intratumoral lymphocytes compared to CD3 epsilon (fig A): #1-normal expression (fig B); #2-reduced expression (fig B)
References: OMIM 186780
Also called endosialin, tumor endothelial marker 1 (TEM1)
Cell surface glycoprotein associated with tumors - traditionally thought present in vascular endothelial cells (Proc Natl Acad Sci USA 1992;89:10832, J Biol Chem 2001;276:7408), but may actually be marker of stromal fibroblasts (FEBS Lett 2005;579:2569)
Not present (or weak) in non-tumor associated endothelium
Uses: no significant clinical use by pathologists
Positive staining (normal): endometrium; embryos (Cancer Res 2001;61:6649), fibroblasts and pericytes during lymphoid tissue development (FEBS Lett 2007;581:3550); RNA at low/moderate levels in many organs
Positive staining (disease): MFH and other sarcomas, some capillaries and fibroblasts in carcinomas; endothelium of high grade brain tumors (J Neuropathol Exp Neurol 2004;63:1274); RNA at low/moderate levels in carcinomas (Cancer Immun 2005 Aug 3;5:10)
Micro images: normal tissue; normal colon and colorectal carcinoma (see TEM1); various tumors #1 (scroll down for color images); #2; #3
References: OMIM 606064
Also called ENPEP, glutamyl aminopeptidase, differentiation antigen gp160, aminopeptidase A
Regulates blood pressure via renin-angiotensin system (J Biol Chem 2006;281:23503)
Uses: no significant clinical use by pathologists
Positive staining (normal): kidney; also brain, heart, liver, lung, placenta, skeletal muscle, pancreas (Genomics 1993;17:657)
Positive staining (disease): cervical neoplasia (Lab Invest 2004;84:639), renal cell carcinoma-some (Proc Natl Acad Sci USA 1993;90:7069)
Micro images: cervical HSIL and squamous cell carcinoma
References: OMIM 138297
Programmed cell death ligand 2; also called B7DC
Involved in the costimulatory signal, essential for T lymphocyte proliferation and interferon gamma production
Found in the plasma membrane
Programmed cell death ligand 1; also called B7-H1
Involved in the costimulatory signal, essential for T lymphocyte proliferation and production of interferon gamma and IL10
Found in the plasma membrane and intracellular membrane
Also called ICOS
Enhances basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, upregulation of molecules that mediate cell-cell interaction and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes
A type I membrane protein
Defects cause ICOS deficiency (MIM:607594), a form of common variable immunodeficiency characterized by recurrent bacterial infections of the respiratory and digestive tracts, but without splenomegaly, autoimmune disease, sarcoid-like granulomas, overt T cell immunodeficiency
Present in: activated T cells, tonsillar T cells, fetal and newborn thymic medulla
References: Swiss-Prot entry
CD281 TLR1_HUMAN Q15399 601194 TLR1 Toll-like receptor 1 (Toll/interleukin-1 receptor-like) (TIL)CD282 TLR2_HUMAN O60603 603028 TLR2; TIL4 Toll-like receptor 2 (Toll/interleukin-1 receptor-like protein 4)CD283 TLR3_HUMAN O15455 603029 TLR3 Toll-like receptor 3CD284 TLR4_HUMAN O00206 603030 TLR4 Toll-like receptor 4CD289 TLR9_HUMAN Q9NR96 605474 TLR9 Toll-like receptor 9
End of CD Markers chapter