Molecular Diagnostics

British Journal of Cancer (2005) 92, 1253–1260. doi:10.1038/sj.bjc.6602499 www.bjcancer.com
Published online 22 March 2005

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

K Mimura1, K Kono1, M Hanawa2, F Mitsui1,2, H Sugai1, N Miyagawa1, A Ooi2 and H Fujii1

  1. 1First Department of Surgery, University of Yamanashi, 1110 Tamaho, Yamanashi 409-3898, Japan
  2. 2First Department of Pathology, University of Yamanashi, Yamanashi 409-3898, Japan

Correspondence: Dr K Kono, E-mail: kojikono@yamanashi.ac.jp

Received 26 October 2004; Revised 26 January 2005; Accepted 8 February 2005; Published online 22 March 2005.

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Abstract

The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies (Herceptin) against HER-2, as immunotherapy for oesophageal cancer, is a novel and attractive approach. It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma (SCC) and to evaluate the relationship between HER-2 status and HLA haplotype, since the candidates for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype. We determined the frequency of HER-2 expression using the HercepTest™ for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation (FISH) assay in oesophageal SCC (n=66). HER-2-positive tumours (1+/2+/3+) analysed by a HercepTest were observed in 30.3% of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0% of all the patients, in which all HercepTest (3+) tumours were found to have gene amplification and three of six moderately positive (2+) tumours showed gene amplification. Furthermore, HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3+ than those who were HercepTest 1+. Moreover, the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group. Also, the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification. In addition, oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours (1+/2+/3+) accounted for 26% of these cases, and both HLA-A2- and HER-2-positive tumours accounted for 18% of them.

Keywords:

HER-2/neu, FISH, immunohistochemistry, HLA, immunotherapy