EPCAM

WP

MIM:185535

HGNC:11529

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell-cell adhesion in epithelia.

EpCAM is also involved in cell signaling, migration, proliferation, and differentiation.

Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc, e-fabp, and cyclins A & E. It appears to play a role in tumorigenesis and metastasis of carcinomas, so it can also act as a potential prognostic marker and as a potential target for immunotherapeutic strategies.

Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker for various cancers.

Pathology

 germline mutations in congenital tufting enteropathy (MIM.613217)

 overexpression in cancers

• positive IHC of peritoneal atypical cells with EPCAM (MOC31) favors metastatic adenocarcinoma over reactive mesothelium
• https://twitter.com/drtylerhickey/status/762757778330914816

 prognosis underexpression in RCC

• A negative EPCAM IHC was found in 1/3 of the patients and was associated with high-grade disease and nodal metastases. (23180689)
• Kaplan-Meier analyses demonstrated a significant association between positive EPCAM IHC and prolonged overall survival, even in a subset of low risk ccRCC. (23180689)
• In multivariable analyses, EPCAM represented an independent risk factor of survival throughout all subgroups. (23180689)
• For localized, low-grade ccRCC, information of EPCAM IHC raised predictive accuracy of a multivariate model by ∼5%, compared to T-stage and grade alone. (23180689)
• EPCAM is an independent prognostic molecular marker in ccRCC and, especially in localized ccRCC, might be able to provide auxiliary information for a better prognostication. (23180689)

IHC

 BerEP4 monoclonal antibody

See also

 SPINT2

• SPINT2-associated tufting enteropathy (20009592)

References

 Epithelial cell adhesion molecule (EPCAM) is an independent prognostic marker in clear cell renal carcinoma. Eichelberg C, Chun FK, Bedke J, Heuer R, Adam M, Moch H, Terracciano L, Hinrichs K, Dahlem R, Fisch M, Schlomm T, Sauter G, Minner S. Int J Cancer. 2012 Nov 26. PMID: 23180689

 Further evidence for EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Schaible T, Szigeti R, Byrd RH, Finegold MJ, Ranganathan S, Gopalakrishna GS, Tatevian N, Kellermayer R. Am J Med Genet A. 2010 Jan;152A(1):222-4. PMID: 20034091

 Further evidence for EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Schaible T, Szigeti R, Byrd RH, Finegold MJ, Ranganathan S, Gopalakrishna GS, Tatevian N, Kellermayer R. Am J Med Genet A. 2010 Jan;152A(1):222-4. PMID: 20034091

 Al-Mayouf, S. M.; Alswaied, N.; Alkuraya, F. S.; AlMehaidib, A.; Faqih, M. : Tufting enteropahty and chronic arthritis: a newly recognized association with a novel EpCAM gene mutation. J. Pediat. Gastroent. Nutr. 49: 642-644, 2009. PubMed ID : 19820410

 Expression of EpCam and villin in Barrett’s esophagus and in gastric cardia. Anders M, Sarbia M, Grotzinger C, Meining A, Hofler H, Wiedenmann B, Rosch T. Dis Markers. 2008;24(6):287-92. PMID: 18688077

 Identification of EpCAM as the gene for congenital tufting enteropathy. Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Gastroenterology. 2008 Aug;135(2):429-37. Epub 2008 May 15. PMID: 18572020

 Limited suitability of EpCAM for molecular staging of tumor borders in head and neck cancer. Andratschke M, Hagedorn H, Luebbers CW, Schmitt B, Lang S, Zeidler R, Wollenberg B. Anticancer Res. 2006 Jan-Feb;26(1A):153-8. PMID: 16475692

 The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Münz M, Zeidler R, Gires O. Cancer Lett. 2005 Jul 8;225(1):151-7. PMID: 15922867

 The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Münz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. Oncogene. 2004 Jul 29;23(34):5748-58. PMID: 15195135

 Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer. Spizzo G, Obrist P, Ensinger C, Theurl I, Dünser M, Ramoni A, Gunsilius E, Eibl G, Mikuz G, Gastl G. Int J Cancer. 2002 Apr 20;98(6):883-8. PMID: 11948467

 The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung. Piyathilake CJ, Frost AR, Weiss H, Manne U, Heimburger DC, Grizzle WE. Hum Pathol. 2000 Apr;31(4):482-7. PMID: 10821496

 Ep-Cam levels in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Poczatek RB, Myers RB, Manne U, Oelschlager DK, Weiss HL, Bostwick DG, Grizzle WE. J Urol. 1999 Oct;162(4):1462-6. PMID: 10492238

 Durbin, H.; Rodrigues, N.; Bodmer, W. F. : Further characterization, isolation and identification of the epithelial cell-surface antigen defined by monoclonal antibody AUAI. Int. J. Cancer 45: 562-565, 1990. PubMed ID : #2307544

 Goulet, O.; Kedinger, M.; Brousse, N.; Cuenod, B.; Colomb, V.; Patey, N.; de Potter, S.; Mougenot, J.-F.; Canioni, D.; Cerf-Bensussan, N.; Ricour, C. : Intractable diarrhea of infancy with epithelial and basement membrane abnormalities. J. Pediat. 127: 212-219, 1995. PubMed ID : 7636644

 Goulet, O. J.; Brousse, N.; Canioni, D.; Walker-Smith, J. A.; Schmitz, J.; Phillips, A. D. : Syndrome of intractable diarrhoea with persistent villous atrophy in early childhood: a clinicopathological survey of 47 cases. J. Pediat. Gastroent. Nutr. 26: 151-161, 1998. PubMed ID : 9481629

 Meyaard, L.; van der Vuurst de Vries, A.-R.; de Ruiter, T.; Lanier, L. L.; Phillips, J. H.; Clevers, H. : The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR). J. Exp. Med. 194: 107-112, 2001. Note: Retraction: J. Exp. Med.::198: 1129 only, 2003. PubMed ID : 11435477

 Perez, M. S.; Walker, L. E. : Isolation and characterization of a cDNA encoding the KS1/4 epithelial carcinoma marker. J. Immun. 142: 3662-3667, 1989. PubMed ID : 2469722

 Reifen, R. M.; Cutz, E.; Griffiths, A.-M.; Ngan, B. Y.; Sherman, P. M. : Tufting enteropathy: a newly recognized clinicopathological entity associated with refractory diarrhea in infants. J. Pediat. Gastroent. Nutr. 18: 379-385, 1994. PubMed ID : 8057225

 Sivagnanam, M.; Mueller, J. L.; Lee, H.; Chen, Z.; Nelson, S. F.; Turner, D.; Zlotkin, S. H.; Pencharz, P. B.; Ngan, B.-Y.; Libiger, O.; Schork, N. J.; Lavine, J. E.; Taylor, S.; Newbury, R. O.; Kolodner, R. D.; Hoffman, H. M. : Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology 135: 429-437, 2008. PubMed ID : 18572020

 Spurr, N. K.; Durbin, H.; Sheer, D.; Parkar, M.; Bobrow, L.; Bodmer, W. F. : Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI. Int. J. Cancer 38: 631-636, 1986. PubMed ID : 3770992

 Strnad, J.; Hamilton, A. E.; Beavers, L. S.; Gamboa, G. C.; Apelgren, L. D.; Taber, L. D.; Sportsman, J. R.; Bumol, T. F.; Sharp, J. D.; Gadski, R. A. :
Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA. Cancer Res. 49: 314-317, 1989. PubMed ID : 2463074

 Szala, S.; Froehlich, M.; Scollon, M.; Kasai, Y.; Steplewski, Z.; Koprowski, H.; Linnenbach, A. J. : Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. Proc. Nat. Acad. Sci. 87: 3542-3546, 1990. PubMed ID : 2333300