Analysis of c-Ki-ras oncogene and p53 immunocytochemistry in the gallbladder mucosa of an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts.

Anomalous arrangement of the pancreaticobiliary ducts is a congenital condition which predisposes the affected person to biliary tract carcinoma. We developed an experimental dog model of anomalous arrangement of the pancreaticobiliary ducts to investigate the mechanism of carcinogenesis in this condition. We used this model to analyze point mutations in the c-Ki-ras gene, and to assess the expression of mutant p53 protein in the gallbladder mucosa. The histopathological appearance of the gallbladder mucosa was also examined. Glandular structures were seen in four of seven (57%) gallbladders examined 14 months after the surgical creation of an anastomosis between the gallbladder and the pancreatic duct. Goblet cells were seen in two of seven gallbladders (29%). However, dot-blot hybridization and immunohistochemical study did not reveal any mutations in the c-Ki-ras gene, or any over-expression of the p53 protein in the specimens. These results show that the gallbladder mucosa is damaged by refluxing pancreatic juice in this dog model of anomalous arrangement of the pancreaticobiliary ducts, but that severe damage may be necessary to induce mutations in the c-Ki-ras proto-oncogene, or in the p53 gene.