Correlation between epidermal growth factor receptor (EGFR) protein expression (PE) and gene amplification (GA) in non-small cell lung carcinoma (NSCLC)

Abstract

7079 Background: Inhibition of EGFR pathway is an established strategy for the treatment of advanced NSCLC. In NSCLC, EGFR expression has been analyzed by immunohistochemistry (IHC) and has not shown any correlation with response to EGFR inhibitors. We evaluated 199 consecutive cases of newly diagnosed NSCLC to determine the correlation between EGFR PE and GA with various clinico-pathological characteristics and survival. Methods: IHC was performed and graded using anti-EGFR mouse monoclonal antibody (DakoCytomation, Carpenter, CA). For GA, FISH analysis was performed using the dual-color EGFR SpectrumOrange/CEP7 SpectrumGreeen probe (Vysis, Downers Grove, IL) and paraffin pretreatment reagent kit (Vysis, Inc., Downers Grove, IL). Average and maximum numbers of EGFR gene copies per cell, average ratio of EGFR gene to chromosome 7 centromere signals (CEP7) and amplification were determined by FISH for each tumor. Amplification was defined as a ratio of EGFR signals to CEP7 of ≥2.0. Results: EGFR PE was more frequent in squamous cell carcinoma (SCC) (26%) than in adenocarcinoma (ADC) (11%) (P=0.0076). EGFR GA was present in 10% of NSCLC. SCC had a higher ratio of CEP7 than ADC (mean ratio 1.95 vs 1.47) (P=0.0005). Of 34 cases with PE (18 SCC, 15 ADC) only 15 (44%) had EGFR GA, and 5 of those without PE demonstrated GA. There was no correlation between EGFR PE/GA with age, gender, stage or survival. Poorly differentiated carcinomas(PDC) demonstrated higher average number of EGFR gene copies/cell (mean 4.10, P=0.032). Higher ratio of EGFR gene to CEP7 was seen in PDC (mean ratio 1.839, P=0.0324) and stage pT1 (mean ratio 1.797, P=0.0243). Conclusions: EGFR PE or GA did not correlate with outcome for NSCLC. Our data indicate that expression of EGFR is regulated by gene amplification in only a small subset of NSCLC. No significant financial relationships to disclose.