Gene amplification and mRNA and protein overexpression of c-erbB-2 (HER-2/neu) in human intrahepatic cholangiocarcinoma as detected by fluorescence in situ hybridization, in situ hybridization, and immunohistochemistry

Background/Aims: The human proto-oncogene c-erbB-2 (also called HER-2/neu) is located on chromosome 17q21-22. There have been no studies on gene amplification or mRNA expression of c-erbB-2 in human intrahepatic cholangiocarcinoma (CC) hitherto. Methods: We investigated c-erbB-2 gene amplification by fluorescence in situ hybridization (FISH), c-erbB2 mRNA expression by ISH, and c-erbB-2 protein expression by immunohistochemistry in 22 archival cases of CC. Results: FISH revealed that c-erbB-2 gene signals were increased in CC. ISH showed that c-erbB-2 mRNA signals were located in the nuclei and cytoplasms of cancer cells and were increased in cancer cells compared with non-cancerous bile ducts where no signals were present. Immunohistochemistry showed that the c-erbB-2 protein was expressed in the cell membrane of cancer cells, and was increased compared with non-cancerous bile ducts where no expression was found. There was a positive significant correlation between c-erbB-2 mRNA and protein expression. Clinicopathologically, there were no correlations between the c-erbB-2 expression and various pathological features. Conclusions: These data suggest that c-erbB-2 gene amplification does occur in CC, and that there is an overexpressed c-erbB-2 protein through the enhanced mRNA expression. The c-erbB-2 gene amplification may be related to the oncogenesis or tumor progression of CC.