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

• Published in: Annals of oncology Vol. 18; no. 5; pp. 892 - 897
• Main Authors: Kim, HJ, Yoo, TW, Park, DI, Park, JH, Cho, YK, Sohn, CI, Jeon, WK, Kim, BI, Kim, MK, Chae, SW, Sohn, JH
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2007; Oxford Publishing Limited (England)
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; Cholangiocarcinoma - surgery; Chromogenic Compounds; chromogenic in situ hybridization; extrahepatic cholangiocarcinoma; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, erbB-2; HER-2/neu; Humans; Immunohistochemistry; In Situ Hybridization; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lymph Nodes - metabolism; Lymphatic Metastasis; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Tumor Burden; Tumors; chromogenic in situ hybridization; HER-2/neu; immunohistochemistry; extrahepatic cholangiocarcinoma; Human; Immunohistochemistry; Prognosis; erbB2 Gene; Gene overexpression; Hepatic disease; Malignant tumor; Biliary tract disease; Chromogenic In Situ Hybridization; Protein; Anatomic pathology; Gene amplification; Malignant cholangioma; C-Onc gene; Digestive diseases; Protooncogene
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdm006

Background: 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. Patients and methods: 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. Results: Overexpression of HER-2/neu protein (staining intensity score ≥ 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). Conclusions: 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.