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Annals of Oncology Advance Access originally published online on February 23, 2007
Annals of Oncology 2007 18(5):892-897; doi:10.1093/annonc/mdm006
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© 2007 European Society for Medical Oncology

gastrointestinal tumors

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

HJ Kim1,*, TW Yoo1, DI Park1, JH Park1, YK Cho1, CI Sohn1, WK Jeon1, BI Kim1, MK Kim2, SW Chae2 and JH Sohn2

1 Department of Internal Medicine
2 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108, Pyung-Dong, Jongro-Ku, Seoul 110-746, South Korea

* Correspondence to: Prof. H. J. Kim, Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital108, Pyung-Dong, Jongro-Ku, Seoul 110-746, South Korea. Tel: +82-2-2001-2060; Fax: +82-2-2001-2049; E-mail: hongjoo3.kim{at}samsung.com

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.

Key words: chromogenic in situ hybridization, extrahepatic cholangiocarcinoma, HER-2/neu, immunohistochemistry

Received for publication October 14, 2006. Revision received January 5, 2007. Accepted for publication January 8, 2007.


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Role of Her-2/neu on extra-hepatic cholangiocarcinoma prognosis: myth or reality ?
Raphael Marechal, et al.
Annals of Oncology, 2 Jul 2007 [Full text]

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