CD Markers CD50 to CD99

Last revised 17 June 2009

Last major update November 2006

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Navigational links to CD markers CD50 to CD99

 

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Go to CD Markers CD 1 to 49

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Primary references

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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://ca.expasy.org/cgi-bin/lists?cdlist.txt

 

CD50

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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

 

CD51

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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

 

CD52

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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

 

CD53

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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

 

CD54

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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

 

CD55

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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

 

CD56

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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 2007;60:981)

Micro images: osteoblasts;  MPNST; plasma cells in myelomas with lytic lesions (CD56+) versus other disorders (CD56-);  pancreatic endocrine neoplasm vs. solid-pseudopapillary tumor (both are CD56+);  nasal cavity (figure 1E)

NK lymphomas - nasal type - nasal cavity; testes (figure 3C) 

other lymphomas - blastic NK lymphoma (figure 3);  blastoid NK lymphoma (figure 5);  CD56+ intestinal T cell lymphoma (figure 1);  NK-like T cell lymphoma of ileum (figure 4)

Flow cytometry images: coexpression of CD56 and CD138 in plasma cell leukemia (not typical);  small cell carcinoma of nasal cavity (figure 1D)

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), small cell carcinoma of 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

 

CD57

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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

 

CD58

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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

 

CD59

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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

 

CDw60

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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

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Not a protein: oligosaccharide present on gangliosides

GD3 - carbohydrate structure

Uses: no significant clinical use by pathologists

 

CD60b

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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

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Not a protein: oligosaccharide present on gangliosides

7-O-acetyl-GD3 - carbohydrate structure

Uses: no significant clinical use by pathologists

 

CD61

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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

 

CD62E

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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

 

CD62L

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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: distribution on neutrophil (confocal microscopy);  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

 

CD62P

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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

 

CD63

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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

 

CD64

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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

 

CD65

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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

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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)

 

CD66a

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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

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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

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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

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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

 

CD66e

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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);  mediastinal neuroendocrine carcinoma;  medullary thyroid carcinoma;  ovarian mucinous and colonic adenocarcinoma;  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);  #2 (porocarcinoma);  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

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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

 

CD67

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Deleted; now CD66b

 

CD68

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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)

 

CD69

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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

 

CD70

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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

 

CD71

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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

 

CD72

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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

 

CD73

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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

 

CD74

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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

 

CD75

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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

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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

 

CDw76

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Renamed CD75s at 7th HLDA Workshop

 

CD77

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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)

 

CDw78

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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

 

CD79a

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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;  lymphoid infiltrate in ileal ulcer;  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

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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

 

CD80

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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

 

CD81

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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

 

CD82

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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);  prostatic adenocarcinoma #1-well differentiated;  #2-poorly differentiated

Positive staining (normal): activated/differentiated hematopoietic cells, endothelial cells, epithelium

Negative staining: erythrocytes

References: OMIM 600623

 

CD83

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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 (