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The Korean Journal of Pathology 2007;41(4): 224-231.
Genetic and Epigenetic Alterations of the Wnt/beta-catenin Signaling Pathway in Cancer of the Ampulla of Vater.
Gwang Il Kim, Jeong Boon Kim, Sang Bum Park, Young Sik Kim, Han Kyeom Kim, Bom Woo Yeom, Yang Seok Chae
1Department of Pathology, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, Seongnam, Korea.
2Department of Pathology, Korea University Medical Center, Seoul, Korea. chaeys21@korea.ac.kr
3Department of Chemistry, College of Natural Science, Dankook University, Cheonan, Korea.
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, beta-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 beta-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 beta-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/beta-catenin signaling pathway during the carcinogenesis of ampullary carcinomas.
Key Words: Ampulla of Vater; Neoplasms; Wnt; APC; Methylation
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