CD Markers
CD44
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: CD44[title]
Related topics: CD44R
CD44
Author: Nat Pernick, M.D.
Topic Completed: 1 October 2013
Minor changes: 2 October 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: CD44[title]
Related topics: CD44R
Table of Contents
Definition / general | Pathophysiology | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative stainingCite this page: Pernick N. CD44. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd44.html. Accessed January 15th, 2021.
Definition / general
- Cell membrane glycoprotein involved in cell-cell interactions, cell adhesion and migration
- Also called CD44s (standard isoform) or CD44H, which lacks all alternative exons; all references below are to standard isoform unless stated otherwise
- Also known as phagocytic glycoprotein 1
- CD44 splicing variants may mediate invasion of trophoblast into maternal tissue in early pregnancy (Eur J Obstet Gynecol Reprod Biol 2006;128:243)
- May help lymphomas disseminate by binding to high endothelial venules
- May be an activity marker in multiple sclerosis (J Neuroimmunol 2005;166:189)
- CD44 splice variants are assumed to have a critical role in the malignant progression of many human tumors, but the clinical significance of CD44 expression is not yet understood
- Enhanced cell surface CD44v6 and v9 expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration (Clin Exp Metastasis 2005;22:663)
- The Indian blood group (OMIM #609027) has antigens In(a) and In(b), which reside on CD44
- Cardiovascular disease: CD44 may induce monocytes to become foamy macrophages and cause atherosclerotic lesions (Biochem Biophys Res Commun 2006;339:846); there is increased expression of CD44 and variants in atheroma and abdominal aortic aneurysm (Am J Pathol 2004;165:1571); high levels on monocytes are associated with coronary arteriogenesis and development of collateral vessels (Circulation 2004;109:1647); closure of ductus arteriosis with wall remodeling involves CD44v6+ smooth muscle cells versus CD44v6 neg smooth muscle cells in patent or closed ductus arteriosis (Am J Cardiol 2006;97:1056)
- References: OMIM #107269
Pathophysiology
- Family of cell surface glycoproteins with numerous isoforms and posttranslational modifications involving glycosylation (CD44v6 is common variant) generated by alternate splicing of mRNA
- Important in epithelial cell adhesion (cell-cell and cell-matrix) to hyaluronate in basement membranes, and maintaining polar orientation of cells; this process may contribute to tissue remodeling and may stimulate cell proliferation and migration
- CD44 also binds hyaluronic acid, laminin, collagen, fibronectin, osteopontin, matrix metalloproteinases and E-selectin / CD62E (J Exp Med 2005;201:1183)
- Also considered a marker of activated B cells
- Important in development of T cells; double negative (CD4-, CD8-) immature thymocytes are divided into developmental stages based on the expression of CD44 and CD25 (Immunol Res 2010;47:45)
- Involved in leukocyte attachment and rolling on endothelial cells, homing to peripheral lymphoid organs (by binding to mucosal addressin, a protein present on high endothelial cells of Peyer’s patches and lymph nodes), and leukocyte chemotaxis and aggregation
Uses by pathologists
- Marker of squamous epithelium
- Expression in flow cytometry may differentiate Burkitt's lymphoma (low) from CD10+ diffuse large B cell lymphoma (Am J Clin Pathol 2010;133:718)
- May help differentiate reactive urothelium (diffuse full thickness staining) from carcinoma in situ (variable basal cell membranous staining, Am J Surg Pathol 2001;25:1074)
Prognostic factors
- In general, loss of CD44 expression is a poor prognostic factor, and expression of particular variants may be a poor prognostic factor for particular diseases
- Breast carcinoma: CD44v7-v8 expression is associated with poor long term prognosis (J Exp Clin Cancer Res 2005;24:75), but CD44s expression is associated with increased disease free survival in node negative patients (Clin Cancer Res 2005;11:3309)
- Carcinoid tumors: loss of CD44s is associated with nodal metastases (Mod Pathol 2002;15:1333)
- Colon carcinoma: high levels of CD44s are associated with responding to treatment (Oncol Rep 2004;11:41)
- Gastrointestinal stromal tumor: in gastric tumors, loss of CD44s is associated with poor clinical outcome (Am J Surg Pathol 2004;28:168)
- Laryngeal carcinoma: reduced expression of CD44 is a poor prognostic factor (Anticancer Res 2005;25:1115)
- Lung carcinoma: reduced CD44v3 expression is associated with poor prognosis in non-small cell lung cancer (Hum Pathol 2000;31:1088)
- Lymphoma: high serum soluble CD44 levels are associated with poor prognosis in non-Hodgkin’s lymphoma (Leuk Res 2002;26:241)
- Melanoma: reduced cell surface CD44 is associated with poor prognosis (Am J Pathol 2000;157:957)
- Myeloma: presence of CD44v9 is associated with poor prognosis
- Neuroblastoma: CD44 is powerful predictive factor for outcome at initial staging - increased levels are associated with better prognosis (J Clin Oncol 1996;14:25, Eur J Cancer 1997;33:2101)
- Ovarian carcinoma: high CD44 expression is associated with favorable outcome (Clin Cancer Res 2003;9:5318)
- Pheochromocytoma: loss of CD44S is associated with metastases (Mod Pathol 2004;17:1119)
- Prostate cancer: loss of CD44 is associated with poor outcome
- Thymoma: increased CD44v5 expression is associated with poorer survival (Ann Thorac Surg 2003;76:213)
- Tongue carcinoma: reduced expression is a poor prognostic factor (Anticancer Res 2003;23:5197)
- Urothelial neoplasms, papillary: loss of CD44 immunoreactivity (restricted to basal cell layer in normal urothelium) is associated with increasing tumor grade and stage in pTa and pT1 patients (Mod Pathol 2000;13:1315)
Microscopic (histologic) images
Images hosted on other servers:
Cutaneous melanoma
(fig B, D)
Ovarian carcinoma
Atheroma and abdominal aortic aneurysm
Breast carcinoma
Positive staining - normal
- Most tissues are CD44+; including astrocyte restricted precursor cells (Dev Biol 2004;276:31), breast myoepithelial cells (CD44v6), colon, lung type II pneumocytes, red blood cells, stomach, urothelial basal cells, uterus and white blood cells
Positive staining - disease
- Colorectal carcinoma (80%)
- Glioma (higher expression in high grade tumors, J Neurooncol 2001;53:115)
- Langerhans cell histiocytosis (Am J Pathol 1994;144:466)
- Oligodendroglioma (Clin Neuropathol 2003;22:169)
- Prostatic small cell carcinoma (Hum Pathol 2009;40:252)
- Pulmonary sclerosing hemangioma (Arch Pathol Lab Med 2005;129:915)
- Sinonasal invasive papilloma (CD44s expression is often lost with invasive disease, Am J Clin Pathol 1998;109:309)
- Squamous cell tumors including adenosquamous carcinoma (standard form and variants, Arch Pathol Lab Med 2000;124:212)
- Thymoma (Ann Thorac Surg 2003;76:213)
- Urothelial carcinoma: simultaneous expression of FAP, CK5/6 and CD44 is a strong prognosticator of disease-specific survival (Hum Pathol 2019;91:61)
Negative staining
- Biliary epithelium, cardiac muscle, hepatocytes (J Clin Pathol 1999;52:730), kidney tubular epithelium, platelets, testis and thymus (CD44s, CD44v5, CD44v6, Ann Thorac Surg 2003;76:213)
- Basal cell carcinoma (downregulation of CD44v6, Hum Pathol 1999;30:1328), esophageal adenocarcinoma, leiomyosarcoma (absent CD44v3 expression, Hum Pathol 2001;32:1190), papillary serous endometrial carcinoma (usually, Int J Gynecol Cancer 2003;13:480), urothelial carcinoma and well-differentiated adenocarcinoma (usually, Am J Surg Pathol 2001;25:1074, but see positive stains)
