EPCAM

About EPCAM

EPCAM on chromosome 2p21 encodes epithelial cell adhesion molecule, a transmembrane glycoprotein expressed in most normal epithelia that mediates calcium independent cell to cell adhesion and also takes part in signaling, proliferation, and maintenance of stem cell properties. Germline deletions removing the last exons of EPCAM, including its polyadenylation signal, cause a form of Lynch syndrome. Because transcription of EPCAM then continues into the adjacent MSH2 gene, the MSH2 promoter becomes methylated and MSH2 is silenced in tissues that express EPCAM, a mechanism reported in 2009. EPCAM deletions account for a small percentage of Lynch syndrome families. Cancer risks in these families depend on the extent of the deletion, with colorectal cancer risk similar to MSH2 carriers and endometrial cancer risk often lower, since silencing is limited to tissues expressing EPCAM. Variants on both copies of EPCAM cause congenital tufting enteropathy, a rare severe intestinal disorder of infancy with intractable diarrhea. EPCAM is highly expressed in many carcinomas and in circulating tumor cells, and it is used as a marker to capture circulating tumor cells and as a target for antibodies, including catumaxomab, and for CAR T cell therapies under investigation.