| Abstract: |
Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. Results: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p < 0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94). Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset. © 2008 The Society of Thoracic Surgeons. |
| Keywords: |
immunohistochemistry; signal transduction; mitogen activated protein kinase; protein kinase b; cancer survival; controlled study; human tissue; protein expression; treatment outcome; aged; disease-free survival; middle aged; survival analysis; retrospective studies; overall survival; histopathology; disease free survival; neoplasm staging; gene overexpression; lung neoplasms; pneumonectomy; epidermal growth factor receptor; tumor markers, biological; smoking; receptor, epidermal growth factor; tumor marker; risk assessment; confidence interval; gene expression regulation, neoplastic; correlation analysis; lung adenocarcinoma; biopsy, needle; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; immunophenotyping; lung alveolus cell carcinoma; adenocarcinoma, bronchiolo-alveolar
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