Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status.
10.4132/KoreanJPathol.2014.48.4.276
- Author:
Jung Ho KIM
1
;
Jeong Mo BAE
;
Kyung Ju KIM
;
Ye Young RHEE
;
Younghoon KIM
;
Nam Yun CHO
;
Hye Seung LEE
;
Mee Soo CHANG
;
Gyeong Hoon KANG
Author Information
1. Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
EPCAM;
DNA mismatch repair;
Microsatellite instability;
Colorectal neoplasms
- MeSH:
Cellular Structures;
Colorectal Neoplasms*;
DNA;
DNA Mismatch Repair;
Immunohistochemistry;
Methylation;
Microsatellite Instability;
Microsatellite Repeats;
Neoplasm Metastasis;
Real-Time Polymerase Chain Reaction
- From:Korean Journal of Pathology
2014;48(4):276-282
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
