Epidermal growth factor receptor and HER-2/neu status by immunohistochemistry and fluorescence in situ hybridization in adenocarcinomas of the biliary tree and gallbladder

Hum Pathol. 2010 Apr;41(4):485-92. doi: 10.1016/j.humpath.2009.10.002. Epub 2009 Dec 29.

Abstract

Adenocarcinomas of the biliary tract and gallbladder are aggressive tumors with a poor prognosis. Standard chemotherapy often offers minimal benefit. 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. This study examines the epidermal growth factor receptor and HER-2/neu expression and the epidermal growth factor receptor gene copy number in biliary tract adenocarcinomas. Fifty-one formalin-fixed, paraffin-embedded cases of adenocarcinomas (26 intrahepatic, 19 extrahepatic, 6 gallbladder) were stained with monoclonal antibodies against epidermal growth factor receptor and HER-2/neu. Fluorescence in situ hybridization analysis was performed in 37 cases using probes directed against epidermal growth factor receptor and centromeric region of chromosome 7. Epidermal growth factor receptor expression was present in 41 (80%) cases, with moderate or strong epidermal growth factor receptor staining in 30 (59%) cases. HER-2/neu was positive in 2 (4%) cases. Fluorescence in situ hybridization analysis showed gain in epidermal growth factor receptor gene copy number in 17 (46%) tumors. Of the latter, 1 showed gene amplification, whereas all others showed gain in chromosome 7, indicating balanced polysomy. Epidermal growth factor receptor overexpression by immunohistochemistry correlated significantly with epidermal growth factor receptor copy number by fluorescence in situ hybridization (P = .02). HER2/neu expression is uncommon in these tumors.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Extrahepatic / metabolism
  • Bile Ducts, Extrahepatic / pathology
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Gallbladder Neoplasms / metabolism
  • Gallbladder Neoplasms / pathology
  • Gene Dosage
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Middle Aged
  • Receptor, ErbB-2 / metabolism*

Substances

  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2