Intrahepatic cholangiocarcinoma arising in chronic advanced liver disease and the cholangiocarcinomatous component of hepatocellular cholangiocarcinoma share common phenotypes and cholangiocarcinogenesis

Abstract

Intrahepatic cholangiocarcinomas (ICCs) are known to arise in cases of non-biliary, chronic advanced liver disease (CALD), but their clinicopathological features remain unexplored. The aim of this study was to compare the histological and immunohistochemical ICCs arising inCALD with those arising in livers with non-specific reactive (NSR) changes. Seventy-one cases of ICC arising in CALD were compared with ICCs arising in livers with NSR changes, including normal livers (72 cases) and the cholangiocarcinomatous (CC) component of hepatocellular cholangioncarcinomas (HC-CCs) (30 cases). The expression of mucin was higher in ICC with NSR changes, whereas it was relatively low in ICC with CALD and the CC component of HC-CC. The expression of biliary markers [cytokeratin (CK)7, CK19, epithelial membrane antigen, and epithelial cell adhesion molecule (EpCAM)] was lower in CC with CALD and in the CC component of HC-CC than in CC with NSR changes. The expression of hepatic progenitor cell markers [neural cell adhesion molecule (NCAM) and c-kit] was higher in ICC with CALD and the CC component of HC-CC than in ICC with NSR changes. EpCAM and CK19 were constantly expressed in cultured CC cells, whereas NCAM was infrequently expressed in cultured CC cells. The carcinogenesis of ICC arising in CALD and the ICC component of HC-CC, each showing similar features, may involve hepatic progenitor cells.