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

J Hepatol. 2002 Jun;36(6):780-5. doi: 10.1016/s0168-8278(02)00057-0.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cholangiocarcinoma / chemistry
  • Cholangiocarcinoma / physiopathology*
  • Female
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Hybridization, Fluorescence
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / physiopathology*
  • Male
  • Middle Aged
  • Proto-Oncogene Mas
  • RNA, Messenger / analysis
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics*

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA, Messenger
  • Receptor, ErbB-2