Genetic and Epigenetic Alterations of the Wnt/ -catenin Signaling Pathway in Cancer of the Ampulla of Vater
김광일, 김한겸, 김영식, 김정분, 박상범, 염본우, 채양석,
소속 상세정보
김광일 ( Kim Gwang-Il )
포천중문의과대학교 분당차병원 병리과
김한겸 ( Kim Han-Kyeom )
고려대학교 의과대학 병리학교실
김영식 ( Kim Young-Sik )
고려대학교 의과대학 병리학교실
김정분 ( Kim Jeong-Boon )
고려대학교 의과대학 병리학교실
박상범 ( Park Sang-Bum )
단국대학교 자연과학대학 화학과
염본우 ( Yeom Born-Woo )
고려대학교 의과대학 병리학교실
채양석 ( Chae Yang-Seok )
고려대학교 의과대학 병리학교실
KMID : 0357920070410040224
Abstract
Background :Carcinoma of the ampulla of Vater is rare and its pathogenesis is unclear. The role of epigenetic changes in the APC or CDH1, in the Wnt pathway, has not been reported in ampullary carcinomas.
Methods :We performed immunohistochemistry on 73 sporadic ampullary carcinomas to identify Wnt-related molecules (APC, -catenin, E-cadherin, c-erbB2, cyclin D1) and examined mutations in the CTNNB1, loss of heterozygosity of 5q21, and the methylation status of the CpG island of APC and CDH1.
Results :Thirteen tumors (17.8%) showed abnormal nuclear localization of -catenin; this was more prominent in the intestinal type than in the pancreaticobiliary type (p=0.01). The loss of APC correlated with the loss of -catenin or c-erb B2 (p<0.01). The prognosis was worse in the group with APC loss than when APC was maintained (p<0.05). There was no mutation identified in CTNNB1. Six (24%) out of 25 informative cases had 5q21 allelic loss. CpG island methylation in APC and CDH1 was detected in 33 (45.2%) and 29 (31.5%) cases, respectively.
Conclusions :The absence of mutations in CTNNB1 and the epigenetic alteration of APC and CDH1, might be characteristic changes in the Wnt/ -catenin signaling pathway during the carcinogenesis of ampullary carcinomas.
키워드
Ampulla of Vater;Neoplasms;Wnt;APC;Methylation
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