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Herceptest: HER2 expression and gene amplification in non-small cell lung cancer
1Department of Medical Oncology, Leicester Royal Infirmary, Leicester, United Kingdom.
Abstract:
HER2 is an erbB/HER type 1 tyrosine kinase receptor that is frequently over-expressed in malignant epithelial tumours. Herceptin, a humanised mouse monoclonal antibody to HER2, is proven therapeutically in the management of metastatic breast cancer, significantly prolonging survival when combined with cytotoxic chemotherapeutic agents. Immunohistochemical studies suggest that non-small-cell lung cancer (NSCLC) tumours may over-express HER2. Our aim was to evaluate HER2 gene amplification and semi-quantitative immuno-expression in NSCLC. A total of 344 NSCLC cases were immunostained for HER2 expression in 2 centres using the HercepTest. Fluorescence in situ hybridisation (FISH) analysis for HER2 gene amplification was performed on most positive cases and a subset of negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno-expression. There was no correlation between immuno-expression and tumour histology or grade. Tumours from higher-stage disease were more often HercepTest-positive (p < 0.001). All 4 HercepTest 3+ cases demonstrated gene amplification. One of the 5 2+ cases tested for gene amplification showed areas of borderline amplification and areas of polyploidy. None of the 19 HercepTest-negative cases demonstrated gene amplification or polyploidy (p < 0.001). Gene amplification was demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene amplification and HER2 protein over-expression assessed by the HercepTest appeared to be uncommon in NSCLC. Herceptin may therefore target only a small proportion of NSCLC tumours and be of limited clinical value in this disease, particularly in the adjuvant setting.
Insights
Human epidermal growth factor receptor 2 (HER2) over-expression is uncommon in non-small-cell lung cancer (NSCLC). Gene amplification was confirmed in all HER2-positive NSCLC cases, suggesting limited clinical value for HER2-targeted therapies like Herceptin.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor frequently over-expressed in malignant epithelial tumors.
- Herceptin, an antibody targeting HER2, is effective in metastatic breast cancer treatment.
- Previous studies suggest potential HER2 over-expression in non-small-cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate HER2 gene amplification and protein immuno-expression in NSCLC.
- To determine the prevalence of HER2 alterations in NSCLC.
- To assess the potential clinical utility of HER2-targeted therapies in NSCLC.
Main Methods:
- Immunohistochemistry (IHC) using the HercepTest on 344 NSCLC cases.
- Fluorescence in situ hybridization (FISH) for HER2 gene amplification on selected cases.
- Correlation analysis between HER2 expression, gene amplification, and clinicopathological features.
Main Results:
- HER2 protein over-expression (2+ or 3+) was observed in 4.3% of NSCLC cases.
- No correlation found between HER2 immuno-expression and tumor histology or grade.
- Higher disease stage correlated with increased HercepTest positivity (p < 0.001).
- All HercepTest 3+ cases showed HER2 gene amplification.
- HER2 gene amplification and protein over-expression were uncommon in NSCLC.
Conclusions:
- HER2 gene amplification and protein over-expression are infrequent in NSCLC.
- HER2-targeted therapies like Herceptin may have limited efficacy in NSCLC.
- Further research is needed to identify specific NSCLC subsets that may benefit from HER2-targeted treatments.