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HER2/neu expression in malignant lung tumors
Fred R Hirsch1, Wilbur A Franklin, Robert Veve
1Lung Cancer Program, Department of Pathology, University of Colorado Cancer Center, Denver, CO 80262, USA.
Abstract:
Despite intensive treatment efforts, the prognosis for lung cancer is very poor; less than 15% of patients survive 5 years. Trastuzumab, a monoclonal antibody targeting the HER2/neu protein receptor, is effective in the treatment of metastatic breast cancer and may be useful in the treatment of non-small cell lung cancer (NSCLC). Using the HercepTest (Dako; Carpenteria, CA), 25% of NSCLC show 2+ or greater HER2/neu expression, but only 6% to 8% of NSCLC tumors have 3+ overexpression. Positive HER2/neu expression is most often seen in adenocarcinomas compared with squamous cell carcinomas or large cell carcinomas, and is rarely seen in small cell lung cancer. As determined by fluorescence in situ hybridization analysis, the high degree of HER2/neu gene expression and gene amplification seen in breast cancer is lower in NSCLC. Polysomy is the cause of increased HER2/neu expression in most NSCLC. Prospective clinical studies with trastuzumab in lung cancer are ongoing. Future studies in NSCLC need to include immunohistochemistry and fluorescence in situ hybridization analysis to determine the method of choice for evaluating clinically relevant HER2/neu-positive tumors.
Insights
Trastuzumab shows potential for treating non-small cell lung cancer (NSCLC) by targeting HER2/neu. While HER2/neu expression varies in NSCLC, further studies are needed to confirm trastuzumab
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer has a poor prognosis despite treatment.
- Trastuzumab, a HER2/neu-targeting antibody, is effective in metastatic breast cancer.
- HER2/neu expression in non-small cell lung cancer (NSCLC) warrants investigation.
Purpose of the Study:
- To evaluate the potential of trastuzumab for treating NSCLC.
- To characterize HER2/neu expression in NSCLC tumors.
- To determine the role of HER2/neu in NSCLC pathogenesis.
Main Methods:
- Immunohistochemistry (HercepTest) to assess HER2/neu protein expression.
- Fluorescence in situ hybridization (FISH) to evaluate HER2/neu gene amplification.
- Analysis of HER2/neu expression across different NSCLC subtypes.
Main Results:
- 25% of NSCLC tumors showed 2+ or greater HER2/neu expression.
- Only 6-8% of NSCLC tumors exhibited 3+ HER2/neu overexpression.
- HER2/neu expression was more common in adenocarcinomas than other NSCLC types.
- HER2/neu gene amplification was less frequent in NSCLC compared to breast cancer; polysomy was the main cause of increased expression.
Conclusions:
- HER2/neu is expressed in a subset of NSCLC, particularly adenocarcinomas.
- Polysomy, not gene amplification, is the primary driver of elevated HER2/neu in NSCLC.
- Prospective studies with trastuzumab in NSCLC are ongoing.
- Combined immunohistochemistry and FISH analysis are crucial for identifying clinically relevant HER2/neu-positive NSCLC.