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Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma
1First Department of Surgery, University of Yamanashi, 1110 Tamaho, Yamanashi 409-3898, Japan.
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.
Insights
HER-2 expression and gene amplification are common in oesophageal squamous cell carcinoma (SCC), correlating with worse survival rates. This highlights potential for HER-2 targeted immunotherapies in SCC patients with specific HLA types.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- HER-2 targeted therapies, including cancer vaccines and antibodies like Herceptin, show promise for oesophageal cancer immunotherapy.
- Understanding HER-2 expression and gene amplification frequencies in oesophageal squamous cell carcinoma (SCC) is crucial for patient selection.
- HER-2 peptide vaccination candidates are often restricted to specific human leukocyte antigen (HLA) haplotypes, necessitating investigation into these associations.
Purpose of the Study:
- To determine the frequencies of HER-2 expression and gene amplification in oesophageal SCC.
- To evaluate the relationship between HER-2 status and HLA haplotype in oesophageal SCC patients.
- To assess the prognostic significance of HER-2 status and gene amplification on patient survival.
Main Methods:
- Immunohistochemistry using HercepTest to assess HER-2 protein expression (1+, 2+, 3+).
- Fluorescence in situ hybridisation (FISH) assay to detect HER-2 gene amplification.
- Analysis of HLA haplotype (specifically HLA-A24 and HLA-A2) in conjunction with HER-2 status.
Main Results:
- HER-2 positivity (1+/2+/3+) was observed in 30.3% of oesophageal SCC cases via HercepTest.
- HER-2 gene amplification was detected in 11.0% of cases by FISH.
- All HER-2 3+ tumours showed gene amplification, and 50% of HER-2 2+ tumours did.
- Poorer survival rates were significantly associated with HER-2 positivity and gene amplification.
- HER-2 positivity occurred in 26% of patients with HLA-A24 and in 18% with HLA-A2.
Conclusions:
- HER-2 expression and gene amplification are prevalent in oesophageal SCC and are linked to adverse patient outcomes.
- These findings support the investigation of HER-2 targeted immunotherapies for oesophageal cancer.
- The association with specific HLA haplotypes (HLA-A24 and HLA-A2) is relevant for selecting patients eligible for HER-2 peptide-based vaccination strategies.
