Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers.
Carcinomas of the biliary tract have a poor prognosis. It is important to understand the molecular genetic characteristics of these tumours in order to employ newer effective treatments and to improve patient prognosis. There is increasing evidence that overexpression of tyrosine kinase growth factor receptors such as ErbB-2, epidermal growth factor receptor (EGFR), and Met may play important roles in the development of biliary tract carcinomas. The aim of this study was to assess the potential for novel chemotherapies targeting these receptors. Overexpression of the tyrosine kinase receptor proteins was examined by immunohistochemistry in 221 biliary tract carcinomas, of which 28 were from the intrahepatic bile duct, 78 from the extrahepatic bile duct, 89 from the gall bladder, and 26 from the ampulla of Vater. Positively stained tumours were further examined for gene amplification by fluorescence in situ hybridization. Overexpression of ErbB-2 was found in 15.7%, 11.5%, and 5.1% of carcinomas of the gall bladder, ampulla of Vater, and extrahepatic bile duct, respectively, and gene amplification was present in 79% of these. Overexpression of EGFR was found in 8.1% of tumours with no predominant location and was also associated with gene amplification with high frequency (77%). Met overexpression, most frequent in intrahepatic bile duct carcinomas (21.4%), was not associated with gene amplification. It is proposed that the new adjuvant chemotherapies could be directed to carcinomas of the biliary tract in which ErbB-2 and EGFR are overexpressed.
Nakazawa
Kumiko
K
Department of Pathology, School of Medicine, University of Yamanashi, Yamanashi, Japan.
Dobashi
Yoh
Y
Suzuki
Shioto
S
Fujii
Hideki
H
Takeda
Yasuhisa
Y
Ooi
Akishi
A
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000473:pathology; D003138:Common Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
D009363:Neoplasm Proteins; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met