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.
OBJECTIVE
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.
Ukita
Yoko
Y
Second Department of Pathology, Tottori University Faculty of Medicine, 86 Nishi-cho, Yonago 683-8503, Japan.
Kato
Masako
M
Terada
Tadashi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000503:physiopathology*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000737:chemistry / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*
D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human