Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients

Abstract

In cholangiocarcinoma (CC), HER-2/neu protein overexpression has rarely been reported and the results are conflicting. The present study aimed to clarify the rates of HER-2/neu protein overexpression and gene amplification in human extrahepatic CC and to evaluate the correlation between HER-2/neu and several clinicopathologic features. We investigated HER-2 gene amplification by chromogenic in situ hybridization (CISH) and HER-2/neu protein overexpression by immunohistochemistry in 55 extrahepatic CC patients who underwent curative surgery at our institution. Overexpression of HER-2/neu protein (staining intensity score > or = 2) was found in 16 out of 55 patients (29.1%). CISH revealed that HER-2 gene signals were increased in 10 out of 55 patients (18.1%). There was a positive and significant correlation between HER-2 gene amplification and HER-2/neu protein overexpression (Spearman's rho = 0.718, P < 0.01). In subgroup with lymph node metastases, HER-2 gene amplification by CISH was significant prognostic factor for survival (OR 43.6, 95% confidence interval 1.6-1219.6). HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases. In subgroup with lymph node metastases who exhibit HER-2/neu overexpression might constitute potential candidates for new adjuvant therapy, such as humanized monoclonal antibodies.