Oncotarget

Research Papers: Pathology:

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

Jung Ho Kim _, Jeong Mo Bae, Young Seok Song, Nam-Yun Cho, Hye Seung Lee and Gyeong Hoon Kang

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Oncotarget. 2016; 7:13372-13387. https://doi.org/10.18632/oncotarget.5618

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Abstract

Jung Ho Kim1,*, Jeong Mo Bae2,*, Young Seok Song3, Nam-Yun Cho3, Hye Seung Lee4, Gyeong Hoon Kang2,3

1Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea

2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

3Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

4Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea

*These authors have contributed equally to this work

Correspondence to:

Gyeong Hoon Kang, e-mail: [email protected]

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.


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