CD Markers - CD100 to CD400

(a) regulates axonal growth cone guidance in the developing CNS through its receptor plexin-B1, which may be related to its expression in invading islands of transformed epithelial cells (but not normal and noninvasive dysplastic epithelium, Proc Natl Acad Sci USA 2006;103:9017)

(b) evokes angiogenic responses from endothelial cells (Blood 2005;105:4321)

(d) after vascular injury, platelet associated CD100 binds to CD100 receptors on nearby platelets to promote thrombus formation (Proc Natl Acad Sci USA 2007;104:1621)

(e) increases CD45 induced T cell adhesion

(f) down regulates B cell expression of CD23

Expression may have prognostic value in soft tissue sarcoma (Cancer 2007;110:164)

Uses: no significant clinical use by pathologists

Positive staining (normal): most hematopoietic cells including platelets, increased expression after T cell activation

Negative staining: immature bone marrow cells

Micro images: head and neck squamous cell carcinoma

References: OMIM 601866, Wikipedia (semaphorins)

CD101

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Also called immunoglobulin superfamily member 2 (IGSF2), V7

Inhibits T cell activation induced by CD3, by (a) inhibiting IL-2RA expression on activated T cells and IL2 secretion (J Immunol 1998;161:209), (b) inducing IL10 production (Eur J Immunol 2000;30:3132)

Uses: no significant clinical use by pathologists

Positive staining (normal): monocytes, granulocytes, dendritic cells, activated T lymphocytes in small intestine

Positive staining (disease): CD4+ CD56+ blastic tumor cells (J Invest Dermatol 2005;124:668), Langerhans cell histiocytosis (Histopathology 2000;36:229)

Micro images: CD4+ CD56+ blastic tumor cells

References: OMIM 604516, J Immunol 1998;161:2780

CD102

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Also called ICAM-2

Binds the leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18)

Provides costimulatory signal in immune response; important in lymphocyte recirculation (J Immunol 2003;171:2588)

Endothelial ICAM-2 mediates angiogenesis (Blood 2005;106:1636)

Elevated serum levels in (a) hemorrhagic fever with renal syndrome (Viral Immunol 2006;19:565) and (b) idiopathic pulmonary fibrosis (Inflammation 2004;28:359)

Uses: no significant clinical use by pathologists

Positive staining (normal): resting lymphocytes, monocytes, platelets, vascular endothelial cells

Positive staining (disease): some lymphomas

Negative staining: neutrophils

References: OMIM 146630

CD103

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Also called human mucosal lymphocyte antigen 1, integrin alpha E beta 7

CD103+ tumor infiltrating lymphocytes have a cytotoxic antitumor effect (J Exp Med 2007;204:559), may play a role in renal allograft rejection (Am J Transplant 2004;4:1026, J Exp Med 2002;196:873)

Uses: marker for hairy cell leukemia, intraepithelial lymphocytes (normal or tumor)

Positive staining (normal): intraepithelial T lymphocytes (90% in GI, tonsil-J Immunol 2005;175:4355, 30% in lung-Clin Exp Immunol 2007;149:162), lamina propria T lymphocytes in the intestine (50%), dendritic cells in gut (J Exp Med 2005;202:1051), rare peripheral blood lymphocytes

Positive staining (disease): hairy cell leukemia (usually, AJCP 2006;125:251), enteropathy-associated T cell lymphoma, splenic marginal zone lymphoma (some)

Flow cytometry images: hairy cell leukemia variant often expresses CD103 but not CD25 #1; #2 (fig C)

References: OMIM 604682

CD104

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Also called integrin beta 4 chain

Tends to associate with alpha 6 subunit (CD49f)

Adhesion receptor (for laminins) in normal epithelia that plays a critical role in structure of hemidesmosomes; associated with intermediate filaments

May contribute to tumor progression (Cancer Metastasis Rev 2005;24:413) via VEGF stimulation (J Cell Biol 2002;158:165)

Overexpressed in pancreatic adenocarcinoma (J Histochem Cytochem 2005;53:799)

Mutations are associated with epidermolysis bullosa with pyloric atresia (Exp Dermatol 2004;13:61)

Uses: no significant clinical use by pathologists

Positive staining (normal): epithelium, thymocytes, Schwann cells

Positive staining (disease): carcinomas (some)

Micro images: normal pancreas and adenocarcinoma

References: OMIM 147557

CD105

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Also called endoglin

Regulatory component of TGF-beta receptor complex; mediates cellular response to TGF-beta 1

Mutations cause Hereditary Hemorrhagic Telangiectasia type I (Am J Hum Genet 1997;61:68)

Required for hemangioblast and early hematopoietic development (Development 2007;134:3041)

Uses: specific and sensitive marker for tumor angiogenesis (better than CD31)

Poor prognostic factor - increased microvessel staining: acute lymphoblastic leukemia in children (Leuk Res 2007 Jun 15; [Epub ahead of print]), breast carcinoma (AJCP 2003;119:374, including node negative-Hum Path 2004;35:176), chronic idiopathic myelofibrosis (Mod Path 2004;17:1513), colorectal carcinoma (Mod Path 2004;17:197), endometrial carcinoma (Gynecol Oncol 2006;103:1007), esophageal adenocarcinoma (Hum Path 2006;37:861), gastric carcinoma (Hum Path 2006;37:861), hepatocellular carcinoma (BMC Cancer 2006;6:110), meningioma (Acta Neuropathol (Berl) 2007;114:147), ovarian carcinoma (Int J Gynecol Cancer 2006;16:1789), primary CNS lymphoma (J Neurooncol 2007;82:249), prostate adenocarcinoma (AJCP 2007;127:572), squamous cell carcinoma of head and neck (Virchows Arch 2006;448:768), including tongue (Laryngoscope 2006;116:1175)

Poor prognostic factor - other: serum endoglin is associated with intrauterine growth retardation during pregnancy (J Clin Endocrinol Metab 2007;92:2831), preeclampsia (N Engl J Med 2006;355:992, Nat Med 2006;12:642), diabetic retinopathy (J Cell Mol Med 2005;9:692)

Tissue endoglin is associated with progressive hepatic fibrosis in chronic HCV infection (J Viral Hepat 2006;13:625) and aortic atherosclerosis (J Atheroscler Thromb 2006;13:82)

Positive staining (normal): activated monocytes, erythroid precursors in marrow; syncytiotrophoblast, cytotrophoblast in first trimester (transient expression)

Positive staining (disease): endometriosis (Reprod Biol 2005;5:51), tumor microvessels (Rom J Morphol Embryol 2007;48:41)

Negative staining: normal endothelial cells (or weak)

Micro images: chronic idiopathic myelofibrosis (fig c, e, f); endometriosis (fig 3-5); liver-normal liver (fig 4); hepatocellular carcinoma #1; #2 and normal liver; lung-non small cell carcinoma (fig D)

References: J Transl Med 2004;2:18

CD106

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Also called VCAM-1 (vascular cell adhesion molecule 1); alpha 4 beta 1 ligand

Interacts with beta 1 integrin VLA4

Adhesion molecular in activated endothelium; plays a role in migration of white blood cells (J Exp Med 2006;203:2763)

May mediate endothelial progenitor cell recruitment to rheumatoid arthritis synovium (Arthritis Rheum 2007;56:1817); associated with type II rheumatic disease (Cell Mol Biol (Noisy-le-grand) 2002;48 Online Pub:OL243)

Important in initiation of atherosclerosis (J Clin Invest 2001;107:1255)

Renal cell carcinoma may exploit VCAM-1 overexpression for immune system escape (Cancer Res 2007;67:6003); on the other hand, down regulation in breast cancer is associated with nodal metastases (Pathol Oncol Res 2002;8:125)

Increased expression: in placentas of women with pregnancy induced hypertension complicated by intrauterine growth retardation (Di Yi Jun Yi Da Xue Xue Bao 2002;22:1022)

Increased plasma levels: associated with: breast cancer [high stage] with circulating cancer cells (Neoplasma 2006;53:538), cancer (general)-early stage or preclinical (Eur J Cancer 2005;41:2355), dengue virus infection severity (J Med Virol 2004;72:445), diabetes with poor control (high HbA1c-Diabetes Care 2007;30:159 or arteriosclerosis obliterans-Clin Chi