Hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma share similar histopathologies, immunophenotypes, and development-related molecules

Abstract

Embryologically, intrahepatic small bile ducts arise from hepatic progenitor cells via ductal plates, whereas the pancreato-extrahepatic biliary progenitor cells expressing the transcription factors PDX1 and HES1 are reportedly involved in the development of the extrahepatic biliary tract and ventral pancreas. The expression of cellular markers characteristic of the different anatomical levels of the biliary tree and pancreas, as well as PDX1 and HES1, was examined in cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma (12 cases), intrahepatic cholangiocarcinoma (21 cases), hilar cholangiocarcinoma (25 cases), and pancreatic ductal adenocarcinoma (18 cases). Anterior gradient protein-2 and S100P were frequently expressed in hilar cholangiocarcinoma and pancreatic ductal adenocarcinoma, whereas neural cell adhesion molecule and luminal expression of epithelial membrane antigen were common in cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma. PDX1 and HES1 were frequently and markedly expressed in pancreatic ductal adenocarcinoma and, to a lesser degree, in hilar cholangiocarcinoma, although their expression was rare and mild in cholangiocarcinoma components in combined hepatocellular cholangiocarcinoma. The expression patterns of these molecules in intrahepatic cholangiocarcinoma were intermediate between those in hilar cholangiocarcinoma and cholangiocarcinoma components of combined hepatocellular cholangiocarcinoma. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma had a similar expression of mucin, immunophenotypes, as well as transcription factors. Pancreatic ductal adenocarcinoma and hilar cholangiocarcinoma showed similar postoperative prognosis. In conclusion, the similar expression of phenotypes related to pancreatobiliary anatomy and embryology may in part explain why these 2 types of carcinoma present similar clinicopathologic features. Further studies on the carcinogenesis of these carcinomas based on their similarities are warranted.