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Investigation of HER2 overexpression in non-small cell lung cancer
Katalin Ugocsai1, László Mándoky, László Tiszlavicz
1Department of Medical Microbiology and Immunbiology, Faculty of General Medicine, University of Szeged, Hungary.
Abstract:
Lung cancer is the leading cause of mortality worldwide. The median survival of advanced disease is in the range of 8 to 10 months. Intrinsic or acquired drug resistance pose major challenges to the success of chemotherapy. The HER2 gene, also known as c-erbB-2 or neu, is a proto-oncogene that encodes a membrane-bound receptor tyrosine kinase of the epithelial growth factor receptor (EGFR) family. It has a possible role in tumor cell proliferation, tumor invasion, tumor metastasis and drug resistance. We retrospectively investigated 88 samples of non-small cell lung cancer (NSCLC) and assessed the correlation between HER2 expression and tumor histology. The expression of HER2 protein was analyzed by immunohistochemical staining (IHC) and HER2 DNA amplification was detected by using fluorescence in situ hybridization (FISH). HER2 overexpression (2+, 3+) was detected in 5 (5.7%) out of 88 specimens. All of the HER2-overexpressing tumors histologically proved to be squamous cell carcinoma (SCC). Cases with 2+ HER2 immunoreactivity showed either no amplification (3.875 and 2.525), or borderline amplification (4.75). Cases with 3+ HER2 immunoreactivity showed moderate amplification (7.35) and strong amplification (15-20 - cluster), respectively. The HER2 expression in NSCLC was relatively low in the selected Hungarian population; consequently, there is no indication for introduction of trastuzumab for the treatment of lung cancer.
Insights
HER2 gene expression is low in non-small cell lung cancer (NSCLC), particularly squamous cell carcinoma. This suggests trastuzumab is not indicated for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer remains a leading global cause of mortality, with advanced stages showing poor prognosis.
- Drug resistance significantly challenges effective chemotherapy for lung cancer.
- The HER2 gene (c-erbB-2/neu) encodes a receptor tyrosine kinase implicated in tumor progression and resistance.
Purpose of the Study:
- To investigate the correlation between HER2 expression and tumor histology in non-small cell lung cancer (NSCLC).
- To assess the potential of HER2 as a therapeutic target in NSCLC.
Main Methods:
- Retrospective analysis of 88 NSCLC samples.
- Immunohistochemical staining (IHC) for HER2 protein expression.
- Fluorescence in situ hybridization (FISH) for HER2 DNA amplification detection.
Main Results:
- HER2 overexpression (2+, 3+) was observed in 5.7% of NSCLC specimens.
- All HER2-overexpressing tumors were histologically identified as squamous cell carcinoma (SCC).
- HER2 expression levels correlated with DNA amplification status, ranging from no amplification to strong amplification in SCC.
Conclusions:
- HER2 expression is relatively low in the studied Hungarian NSCLC population.
- The findings do not support the use of trastuzumab for NSCLC treatment.
- HER2 status may be relevant for specific NSCLC subtypes like SCC.