Molecular analysis of bile duct cancer associated with PBM

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Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder. Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Positivity of p53 was more frequent and stronger in gallbladder carcinoma and in gallbladder epithelium associated with pancreaticobiliary maljunction. These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobilary maljunction and that oxidative DNA injury is related to carcinogenesis of gallbladder carcinoma in patients with pancreaticobiliary maljunction.