CD Markers CD50 to CD99
Last revised 15 May 2008
Last major update November 2006
Copyright © 2001-2008 PathologyOutlines.com, Inc.
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Navigational links to CD markers CD50 to CD99
Go to CD Markers CD 1 to 49
Go to CD Markers CD 100 to 300
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://ca.expasy.org/cgi-bin/lists?cdlist.txt
Also known as ICAM-3, the third counter receptor for LFA-1 (CD54)
Provides adhesion signals important in B-T cell interactions and regulates leukocyte morphology
May predict resistance to radiation therapy in cervical cancer (Int J Cancer 2005;117:194)
Costimulator for HIV1 replication (J Virol 2004;78:6692, J Virol 2002;76:32)
Uses: no significant clinical use by pathologists
Positive staining (normal): leukocytes including eosinophils (J Allergy Clin Immunol 2003;111:1024) and mast cells (Cell Adhes Commun 1999;7:195), epidermal Langerhans cells (J Invest Dermatol 1995;104:995), endothelial cells (J Vasc Res 2004;41:28)
Positive staining (disease): synovium in rheumatoid arthritis (Arthritis Rheum 2003;48:360)
Negative staining: non-hematopoietic cells, platelets (J Clin Invest 1994;94:1243)
References: OMIM 146631
Also called integrin alpha chain V or vitronectin receptor-alpha chain
Integrins are membrane receptors for extracellular matrix-mediated cell adhesion and migration, cytoskeletal organization, cell proliferation, cell survival and differentiation
Integrins are composed of an alpha chain and a beta chain
Alpha-V integrins are a subset of integrins with a common alpha-V subunit combined with beta subunits 1, 3, 5, 6 or 8
The beta chain of the vitronectin receptor is CD61
Most alpha-V integrins recognize the RGD (Arg-Gly-Asp) sequence in various ligands such as vitronectin, fibronectin, osteopontin, bone sialoprotein, thrombospondin, fibrinogen, von Willebrand factor, tenascin or agrin
Alpha V beta 3 integrin may mediate melanoma progression (Oncogene 2005;24:4710)
CD51 on some dendritic cells serves as adenovirus receptor (J Leukoc Biol 2006;79:1271)
Uses: no significant clinical use by pathologists
Positive staining (normal): endothelial cells, megakaryocytes, osteoclasts (Histochemistry 1991;96:169), monocytes and macrophages, placenta cytotrophoblast and Hofbauer cells (Acta Histochem 2003;105:253), fibroblasts
Positive staining (disease): osteoclast disorders including osteoclast-like giant cell neoplasms (Mod Path 2006;19:161) and inflamed synovium (Ann Rheum Dis 1993;52:182)
Negative staining: cartilage (Ann Rheum Dis 2000;59:448)
References: OMIM 193210
Also called Campath-1 and epididymal secretory protein E5
CD52 antibodies are lytic for target cells, both with human complement and via antibody dependent cellular cytotoxicity
Uses: antibodies (Alemtuzumab) are used for long-term depletion of T lymphocytes from donor marrow to prevent graft versus host disease (Bone Marrow Transplant 2000;26:69, Transplantation 1999;67:620); also to treat refractory CLL; high serum levels are poor prognostic marker in CLL (Cancer 2004;101:999); may treat other malignancies (see CD52+ disorders below), including pure red blood cell aplasia (Br J Haematol 2003;123:278); differentiates eosinophils (CD52++) from neutrophils (CD52 weak/negative)
Micro images: figures 1A/B: normal tonsil shows lymphocytic staining, but there is no staining of connective tissue or vessels; C: follicular lymphoma is CD52+; D: Reed-Sternberg cells (arrows) are CD52-; figures 2A/B: SLL/CLL is CD52+; C: anaplastic lymphoma is CD52+; D: adult T cell leukemia/lymphoma is CD52+
Positive staining (normal): thymocytes, lymphocytes, monocytes/macrophages, eosinophils, mast cells (Clin Lymphoma Myeloma 2006;6:478), epithelial cells lining the male reproductive tract
Positive staining (disease): most lymphoid malignancies (variable levels, J Clin Path 1994;47:313), including lymphoplasmacytic lymphoma (100%, AJCP 2005;124:414), myeloma (5-10%, AJCP 2004;121:482), hairy cell leukemia (Am J Hematol 2003;74:227); T cell large granular lymphocytic leukemia (Leuk Lymphoma 2005;46:723), Langerhans cell histiocytosis (Pediatr Blood Cancer 2005;44:251)
Negative staining: neutrophils, Langerhans cells (normal), lymphocytes in paroxysmal nocturnal hemaglobinuria, Reed-Sternberg cells in Hodgkin’s lymphoma
References: OMIM 114280
Most specific and reliable pan-leukocyte marker
Encodes member of tetraspanin family, a cell surface protein with 4 hydrophobic domains that mediate signal transduction
Also has adhesion/activation functions
Upregulated in macrophages exposed to lipopolysaccharide (Mol Cells 2004;17:125)
May transduce CD2-generated signals in T cells and natural killer cells
May be a thymocyte selection marker, with CD69 (Int Immunol 2002;14:249)
Familial deficiency is associated with recurrent infectious diseases (Clin Diagn Lab Immunol 1997;4:229)
Uses: no significant clinical use by pathologists
Positive staining (normal): leukocytes; also dendritic cells, osteoclasts and osteoblasts, mesangial cells (Kidney Int 2003;63:534)
Positive staining (disease): radioresistant tumor cells
Negative staining: platelets, red blood cells, non-hematopoietic cells
References: OMIM 151525
Also called ICAM-1 (intercellular adhesion molecule 1)
Ligand for LFA-1 (CD50)
Receptor for rhinovirus (Proc Natl Acad Sci USA 1991;88:7993), malaria infected erythrocytes (Infect Immun 2006;74:3262, Proc Natl Acad Sci USA 2000;97:1766)
Involved in adhesion of neutrophils to endothelium at site of inflammation
Reacts with CD11a / CD18 or CD11b / CD18 resulting in immune reaction or inflammation
Reduced expression in endometrial cells may contribute to endometriosis (Immunol Lett 2002;80:49)
Uses: CD54 negative gastric carcinoma cells may predict nodal metastases (Dig Dis Sci 2005;50:2224); low CD54 levels associated with poor prognosis in childhood ALL (Br J Biomed Sci 2003;60:149)
Micro images (Mod Path subscribers): keratoacanthoma; poorly differentiated squamous cell carcinoma
Positive staining (normal): broad, B and T cells and B cell precursors, monocytes, osteoclasts, endothelial cells, epithelial cells (various)
Positive staining (tumors): keratoacanthoma (more in fully developed lesions with inflammatory infiltrate), cutaneous squamous cell carcinoma (focal if well differentiated, intense if poorly differentiated, Mod Path 2003;16:8)
Negative staining (tumors): intravascular B cell lymphoma
References: OMIM 147840
Also called complement decay accelerating factor (DAF)
Gene encodes Cromer blood group (Blood Group Antigen Gene Mutation Database)
Binds C3bBb (alternative pathway convertase) and C4b2a (classical pathway convertase) to accelerate decay of the C3 convertases; protects against inappropriate complement activation (J Biol Chem 2005;280:2569)
Receptor for CD97, echovirus (Proc Natl Acad Sci USA 2002;99:10325) and Coxsackie B virus (J Virol 1998;72:9407)
Also is part of lipopolysaccharide-induced receptor complex (Eur J Immunol 2003;33:1399)
Genetic defects that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria (PNH); also cause defective platelets, granulocytes, erythrocytes and possibly lymphocytes
CD55 deficiency is common in patients treated with Campath (anti-CD52), which may predispose to PNH (Transplant Proc 2006;38:1750)
A minor population of CD55-CD59 negative granulocytes and red blood cells predicts a good response to immunosuppressive therapy in patients with acquired aplastic anemia (Blood 2006;107:1308)
Loss of CD55 is associated with poor prognosis in breast cancer (Clin Cancer Res 2004;10:2797); however high expression is associated with poor prognosis in colorectal carcinoma (Cancer Immunol Immunother 2003;52:638)
Case reports: pregnant woman with thrombocytopenia due to PNH
Uses: diagnosis of PNH (AJCP 2006;126:781)
Micro images: breast carcinoma staining #1; #2; #3
Positive staining (normal): all hematopoietic cells and all cell types in intimate contact with complement proteins; also epithelial cells lining extracellular compartments, body fluids, extracellular matrix
References: OMIM 125240
Also called 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), 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-)
Micro images: metanephric adenoma (figure E); large granular lymphocytic leukemia
Positive staining (normal): NK subset, T cell subset, neuroectodermal tissue, retina, brain, prostate, renal proximal tubules
Positive staining (disease): leukemia/lymphomas - autoimmune lymphoproliferative syndrome, hepatosplenic T cell lymphoma (some), nodular lymphocyte predominant Hodgkin lymphoma (CD57+ rosettes in 50%, AJCP 2003;119:192), pre T-ALL (occasional), T-cell large granular lymphocytic leukemia (some)
nerve sheath origin lesions - benign epithelioid nerve sheath tumor (AJSP 2005;29:39), chordoma, dendritic cell neurofibroma with pseudorosettes (AJSP 2001;25:587), melanotic neuroectodermal tumor of infancy, MPNST (expression decreases with tumor grade, AJSP 2003;27:1337), nerve sheath myxoma (AJSP 2005;29:1615),
Positive staining (tumors): other - carcinoid tumors, desmoplastic nested spindle cell tumor of liver (AJSP 2005;29:1), desmoplastic small round cell tumor (AJSP 1998;22:1314), germ cell tumor (embryonal carcinoma, seminoma), mesenchymal chondrosarcoma, metanephric adenoma (AJSP 2001;25:1290), neuroendocrine carcinoma of prostate (AJSP 2006;30:684) and other sites, PNET, prostatic adenocarcinoma, renal carcinoid, renal clear cell carcinoma (some), small cell carcinoma of lung and other sites, spindle cell thymoma (AJSP 2001;25:111), synovial sarcoma, thyroid papillary carcinoma (Cancer 2006;108:331)
Negative staining: B cells, monocytes, red blood cells, platelets; NK/T cell lymphoma-nasal type, Wilm’s tumor
References: OMIM 151290
Also called LFA-3 (lymphocyte function associated antigen)
Ligand for CD2 (J Mol Biol 2001;312:711)
Mediates adhesion between NK cells and target cells (J Immunol 2003;170:294), antigen presenting cells and T cells (Cell 1999;97:791), thymocytes and thymic epithelial cells
High serum levels in Hepatitis B, associated with liver cell damage (World J Gastroenterol 2006;12:4237)
Uses: detect minimal residual disease in pre-B ALL (Haematologica 2003;88:1245)
Micro images: various images; lymphoma (type unknown)
Positive staining (normal): leukocytes (but not mature B cells), pre B cells, erythrocytes, endothelial cells, epithelial cells, fibroblasts, cardiac muscle (J Clin Path 1990;43:893)
Positive staining (disease): pre-B ALL (AJCP 2005;123:119)
Negative staining: mature B cells
References: OMIM 153420
Also called protectin, complement regulatory molecule
Regulates complement mediated cell lysis by inhibiting formation of membrane attack complex (MAC); binds to C8 or C9 components, preventing incorporation of multiple copies of C9 required for complete formation of osmolytic core
Also makes cells susceptible to NK cell mediated cytotoxicity (J Immunol 2006;176:2915)
Genetic defects that reduce both CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria (PNH); also cause defective platelets, granulocytes, erythrocytes and possibly lymphocytes
Low CD59 levels may also cause PNH-like symptoms after Campath therapy (Transplant Proc 2006;38:1750)
Not a particularly good marker for detecting PNH+ monocytes (AJCP 2006;126:781)
In diabetes, glycation may inhibit CD59, causing MAC deposition in vessels, leading to vascular complications (Diabetes 2004;53:2653)
Naegleria (Infect Immun 2006;74:1189), Borrelia (J Immunol 2003;170:3214) and HIV (J Gen Virol 1997;78:1907) may resist complement mediated lysis via a surface CD59 like protein
Uses: no significant clinical use by pathologists
Positive staining (normal): most cells
Positive staining (disease): squamous cell carcinoma of head and neck (J Oral Path Med 2006;35:560)
References: OMIM 107271
Use of CD60, CDw60 and CD60a, CD60b and CD60c is inconsistent
Not proteins, but oligosaccharides present on gangliosides
CD60a: GD3 - carbohydrate structure
CD60b: 9-O-acetyl-GD3 - carbohydrate structure
CD60c: 7-O-acetyl-GD3 - carbohydrate structure
Antibodies provide costimulatory signals for T cells
Expressed on most T cells in autoimmune lesions (Immunol Invest 2001;30:67)
CD8+ CD60+ T cells may regulate IgE memory responses and isotype switching (Hum Immunol 2005;66:1029)
Associated with Th1 immune response in skin (Br J Dermatol 2003;149:739)
Uses: no significant clinical use by pathologists
Positive staining (normal): platelets, T cells (30%, Carbohydr Res 2000;329:791), thymic epithelium, activated keratinocytes, melanocytes, synovial fibroblasts, glomeruli, smooth muscle cells, astrocytes; also epithelium of reproductive system, exocrine and endocrine glands (Histochem J 2000;32:447)
Positive staining (disease): T cells in rheumatoid arthritis and psoriasis, monocytes in cutaneous T cell lymphoma (Acta Derm Venereol 2001;81:263)
Negative staining: B cells, granulocytes, monocytes
References: glycolipids
CD60a
Not a protein: oligosaccharide present on gangliosides
GD3 - carbohydrate structure
Uses: no significant clinical use by pathologists
CD60b
Not a protein: oligosaccharide present on gangliosides
9-O-acetyl-GD3 - carbohydrate structure
May protect tumor cells from apoptosis (