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Epidermal Growth Factor Receptor Messenger RNA Expression, Gene Dosage, and Gefitinib Sensitivity in Non–Small Cell Lung Cancer

2006; American Association for Cancer Research; Volume: 12; Issue: 10 Linguagem: Inglês

10.1158/1078-0432.ccr-06-0106

1557-3265

Rafał Dziadziuszko, Samir E. Witta, Federico Cappuzzo, Seong-Jin Park, Koji Tanaka, Peter V. Danenberg, Anna E. Barón, Lucio Crinó, Wilbur A. Franklin, Paul A. Bunn, Marileila Varella‐Garcia, Kathleen D. Danenberg, Fred R. Hirsch,

Colorectal Cancer Treatments and Studies

Abstract Purpose: Epidermal growth factor receptor (EGFR) mRNA expression and EGFR gene dosage by quantitative PCR in tumor samples obtained from patients with gefitinib-treated non–small cell lung cancer were analyzed in order to determine the association with treatment outcome, clinical, and biological features [EGFR copy number by fluorescent in situ hybridization (FISH), EGFR tyrosine kinase mutations, and EGFR protein expression]. Experimental Design: EGFR mRNA expression was measured by real-time quantitative reverse transcription-PCR in 64 patients, and EGFR gene dosage was analyzed by real-time quantitative PCR in 82 patients from paraffin-embedded specimens. Results: EGFR mRNA expression was higher in responders to gefitinib as compared with nonresponders (P = 0.012). Patients with high EGFR mRNA expression (>5.01) had 43% response probability, whereas patients with low EGFR mRNA expression had 8% response probability (P = 0.006). Patients with high EGFR mRNA expression had longer median progression-free (5.3 versus 2.8 months, P = 0.028) but not overall survival (13.8 versus 10.9 months, P = 0.87). EGFR mRNA expression was higher in FISH-positive patients (P = 0.001) and in patients with positive EGFR immunostaining (P < 0.001) but not in patients with EGFR mutations (P = 0.19). EGFR gene dosage did not predict response (P = 0.54), progression-free (P = 0.73), or overall survival (P = 0.89). EGFR gene dosage was not associated with FISH positivity (P = 0.15), relative mRNA expression (P = 0.27), EGFR mutation status (P = 0.39), and EGFR protein expression (P = 0.35). Conclusion: EGFR mRNA expression is a predictive biomarker for response to gefitinib and to progression-free survival after gefitinib treatment. EGFR gene dosage is neither predictive for response nor progression-free nor overall survival.