CD Markers CD50 to CD99-Printer Friendly Version
Last revised 29 December 2006
Copyright © 2001-2006 PathologyOutlines.com, Inc.
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Primary references
American Journal of Clinical Pathology (AJCP), August 1975 to November 2006
American Journal of Surgical Pathology (AJSP), March 1977 to November 2006
Archives of Pathology and Lab Medicine (Archives), January 1976 to September 2006
Human Pathology (Hum Path), March 1970 to November 2006
Modern Pathology (Mod Path), January 1988 to November 2006
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
Sternberg,
S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins,
2004
University
of Pittsburgh Medical Center Case Reports
CD Marker websites: http://www.hlda8.org/HLDAtoHCDM.htm, http://ca.expasy.org/cgi-bin/lists?cdlist.txt
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Images are particularly needed for these CD markers: CD50, CD51, CD53, CD59, CD60, CD64, CD65, CD66c, CD66d, CD66f, CD69, CD72, CD73, CD75s, CD77, CDw78, CD81, CD84, CD85A-M, CD89, CD92, CD96, CD98
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)
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)
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)
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 N-CAM (neural cell adhesion molecule)
Nerves: regulates homophilic (like-like) interactions between neurons and between neurons and muscle; associates with fibroblast growth factor receptor and stimulates tyrosine kinase activity of receptor to induce neurite outgrowth; when neural crest cells stop making N-CAM and N-cadherin, and start displaying integrin receptors, cells separate and migrate (Cell Sci 2002;115:283)
Hematopoiesis: prototypic marker of NK cells, also present on subset of CD4+ and CD8+ T cells
Adhesion: contributes to cell-cell or cell-matrix adhesion during development
Prognostic factor: CD56 negative myeloma has poor prognosis (Leuk Lymphoma 2004;45:61)
Case reports: 6 year old girl with B-ALL and CD56 and CD57 coexpression (Pediatr Hematol Oncol 2004;21:677), CD56+ plasma cell leukemia
Uses: marker for NK cells and NK lymphomas; differentiates plasma cells in myeloma (CD56+) from reactive plasmacytosis or MGUS (CD56-, Am J Path 2002;160:1293); detect neuroendocrine disorders (J Clin Path 2002;55:535), particularly if extensive crush artifact (J Clin Path 2005;58:978), defines cutaneous lymphoproliferative disorders with poor prognosis, other than cutaneous T cell lymphoma, J Clin Pathol 2006 Oct 3; [Epub ahead of print])
Positive staining (normal): NK cells (80-90%), large granular lymphocytes, activated T cells, osteoblasts; cerebellum and cortex at neuromuscular junctions, neuroendocrine tissue and neurons (membranous pattern), glia; skeletal muscle
Positive staining (disease) - leukemia/lymphoma - acute myeloid leukemia (some), cutaneous lymphoproliferative disorders, granulocytic sarcoma (variable), myeloma, NK/T cell lymphomas, T cell lymphomas (various)
Positive staining (disease): other - cardiac ischemic damage (Verh Dtsch Ges Path 2004;88:246), extrahepatic biliary atresia (AJSP 2003;27:1454), Merkel cell carcinoma (J Dermatol Sci 2003;31:219), mesotheliomas (some), neuroblastoma (adult), neuroendocrine carcinomas (AJSP 2006;30:684), pancreatic acinar cell carcinoma, pancreatic solid pseudopapillary tumor (Mod Path 2006;19:1409), pheochromocytoma, small cell carcinoma of cervix (Int J Gynecol Path 2005;24:113), lung and prostate (AJSP 2006;30:705), sustentacular cell tumor (AJSP 2006;30:268), synovial sarcoma (usually, Mod Path 2006;19:659), thyroid carcinoma (AJCP 2003;120:64), Wilm’s tumor
Negative staining: granulocytes, monocytes, B cells; ALL, large granular NK cell lymphocytosis, (some cases, Am J Path 2004;165:1117), plasma cell leukemia, PNET/Ewing’s sarcoma
References: OMIM 116930
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-)
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)
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)
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
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
CD62L
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: no significant clinical use by pathologists
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, summary of clinical studies
CD62P
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 2006 Oct 16; [Epub ahead of print])
Uses: distinguishing heparin-induced thrombocytopenia without and with thrombosis (Thromb Haemost 1999;82:1255)
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)
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
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)
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
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: polyclonal CEA is 92% sensitive for metastases vs. 0% for bile duct adenoma (AJSP 2005;29:381)
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
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)
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); staining protocol
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+)
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
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
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)
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)
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)
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), staining protocol
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)
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
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)
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
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
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
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
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)
Uses: no significant clinical use by pathologists
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
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
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
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)
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)
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
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
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)
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
Go to CD Markers CD 1 to 49
Go to CD Markers CD 100 to 300
End of CD markers CD 50 to CD99