Korean J Pathol.  2007 Aug;41(4):224-231.

Genetic and Epigenetic Alterations of the Wnt/beta-catenin Signaling Pathway in Cancer of the Ampulla of Vater

• Kim GI
• Kim JB
• Park SB
• Kim YS
• Kim HK
• Yeom BW
• Chae YS

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.

Keyword

Ampulla of Vater; Neoplasms; Wnt; APC; Methylation

MeSH Terms

Ampulla of Vater*
beta Catenin
Cadherins
Carcinogenesis
CpG Islands
Cyclins
Epigenomics*
Immunohistochemistry
Loss of Heterozygosity
Methylation
Prognosis
Wnt Signaling Pathway
Cadherins
Cyclins
beta Catenin