Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status
김정호, 배정모, 김경주, Rhee Ye-Young, 김영훈, 조남윤, 이혜승, 장미수, 강경훈,
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김정호 ( Kim Jung-Ho )
SMG-SNU Boramae Medical Center Department of Pathology
배정모 ( Bae Jeong-Mo )
Seoul National University College of Medicine Department of Pathology
김경주 ( Kim Kyung-Ju )
Seoul National University College of Medicine Department of Pathology
( Rhee Ye-Young )
Seoul National University College of Medicine Department of Pathology
김영훈 ( Kim Young-Hoon )
Seoul National University College of Medicine Department of Pathology
조남윤 ( Cho Nam-Yun )
Seoul National University College of Medicine Cancer Research Institute
이혜승 ( Lee Hye-Seung )
Seoul National University Bundang Hospital Department of Pathology
장미수 ( Chang Mee-Soo )
SMG-SNU Boramae Medical Center Department of Pathology
강경훈 ( Kang Gyeong-Hoon )
Seoul National University College of Medicine Department of Pathology
KMID : 0357920140480040276
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.
키워드
EPCAM; DNA mismatch repair; Microsatellite instability; Colorectal neoplasms
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