Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma

// Jung Ho Kim 1, * , Jeong Mo Bae 2, * , Young Seok Song 3 , Nam-Yun Cho 3 , Hye Seung Lee 4 , Gyeong Hoon Kang 2, 3 1 Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea 2 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea 3 Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea 4 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea * These authors have contributed equally to this work Correspondence to: Gyeong Hoon Kang, e-mail: ghkang@snu.ac.kr Keywords: EPCAM, immunohistochemistry, colorectal cancer, lynch syndrome, prognosis, Pathology Section Received: March 15, 2015      Accepted: September 08, 2015      Published: October 30, 2015 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.