Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas

Abstract

Hepatic cholangiocarcinomas are tumors with poor prognosis and with increasing incidence worldwide. The aim of the study was to compare morphological features and protein profiles of hilar and peripheral cholangiocarcinomas. Clinicopathological data were collected from 111 cholangiocarcinomas (59 peripheral and 52 hilar). Protein expression, assessed on tissue samples using tissue microarray and protein array technologies, was compared between both types of tumors and with extrahepatic cholangiocarcinoma and hepatocholangiocarcinoma. Hilar cholangiocarcinomas were smaller in size (mean: 2.7 vs. 8 cm, p<0.001), were more often well differentiated adenocarcinomas (65% vs. 36% well differentiated, p<0.01) and carried out stronger perineural invasion (83% vs. 42%, p<0.001) than peripheral cholangiocarcinomas. Regarding protein expression, hilar cholangiocarcinomas more often expressed MUC5AC (62% vs. 22%, p<0.0001), Akt2 (54% vs. 27%, p<0.001), CK8 (98% vs. 81%, p<0.005) and annexin II (92% vs. 66%, p<0.001). Interestingly, VEGF A expression was more frequently encountered in peripheral cholangiocarcinoma (69% vs. 25%, p<0.0001) and correlated with increased vascular density. Using protein array antibody, we identified filamin A as significantly overexpressed (>2-fold) in peripheral cholangiocarcinomas. Our results show that hilar and peripheral cholangiocarcinomas display specific protein profiles, especially regarding VEGF expression. This suggests a potential benefit for anti-angiogenic therapies in peripheral hepatic CCs.