title: Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma.
abstract: We aimed to comprehensively investigate the clinicopathologic and molecular implications of altered epithelial cell adhesion molecule (EPCAM) expression in colorectal carcinoma (CRC). EPCAM immunohistochemical expression, EPCAM 3' end deletion, EPCAM promoter methylation, microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP) were analyzed in large cohorts of human CRCs. Among 218 MSI-high CRCs, complete loss (CL) of EPCAM expression was observed in two cases, both of which displayed MSH2 deficiency and EPCAM 3' deletion. Thirty-one of the 218 MSI-high CRCs demonstrated the partial loss (PL) of EPCAM expression without EPCAM deletion or methylation and were correlated with CIMP-high and poor disease-free survival. Histologically, foci exhibiting EPCAM loss in EPCAM-PL tumors were dominantly distributed in poorly differentiated tumor components and/or in the invasive tumor front. The implications of EPCAM-PL were further validated in a consecutive series of 726 CRCs. EPCAM-PL (n = 50; 6.9%) was also associated with CIMP-high and adverse pathologic factors and was confirmed to be an independent poor prognostic factor in CRC (HR, 1.57; 95% CI, 1.04 to 2.39). EPCAM-CL can be used to screen for EPCAM deletion-induced Lynch syndrome-associated CRC, whereas EPCAM-PL can be used as an indicator of tumor aggressiveness and poor prognosis in CRC.
authors.affiliation: Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Song
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.|Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: EPCAM; Lynch syndrome; Pathology Section; colorectal cancer; immunohistochemistry; prognosis