In this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer.
Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations and HER2 receptors hold great promise for improving the future management of cholangiocarcinoma.
Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period.
Multiplex immunostaining/tissue cytometry and immunoprecipitation studies showed: 1) BRK co-localized with EGFR and ErbB2/neu; 2) BRK(high)/EGFR(high)-co-expressing CC cells had significantly higher Ki67 labeling and; 3) stronger BRK protein expression was seen in perihilar and distal CC than intrahepatic CC and directly correlated with CC differentiation.
Because epidermal growth factor receptor and HER-2/neu antagonists have been successfully used in adenocarcinomas from other sites, their use in cholangiocarcinoma can be potentially beneficial.
HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases.
HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases.
Moreover c-erbB-2 mRNA was not detected in seven hepatocellular carcinomas examined by Northern blot analysis. c-erbB-2 overexpression is, therefore, unlikely to be contributing to the malignant phenotype in hepatocellular carcinoma and cholangiocarcinoma.
Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation.