Concurrence of EGFR amplification and sensitizing mutations indicate a better survival benefit from EGFR-TKI therapy in lung adenocarcinoma patients

Abstract

Objectives: Tumor heterogeneity, which causes different EGFR mutation abundance, is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. Frequent EGFR amplification and its common affection in EGFR mutant allele promote the hypothesis that EGFR mutant abundance might be determined by EGFR copy number variation and therefore examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment.

Materials and methods: In this study, 86 lung ADC patients, who harbored EGFR activating mutations and received EGFR-TKI treatment, were examined for EGFR amplification and expression by Dual-color Silver in situ Hybridization (DISH) and immunohistochemistry analysis, respectively.

Results and conclusion: Forty-one of 86 (47.7%) samples with EGFR activating mutations were identified with EGFR amplification. Patients with EGFR gene amplification had a significantly longer PFS than those without (16.3 vs. 9.1 months, p=0.004). The EGFR expression was then examined by immunohistochemistry analysis. Thirty-nine of 86 (45%) tumors had EGFR overexpression, which was significantly correlated with EGFR amplification (p=0.000). However, patients with EGFR overexpression exhibited no difference in PFS (14.1 vs. 13.3 months, p=0.797). In conclusion, EGFR amplification occurs frequently in lung ADC patients harboring EGFR activating mutations, and could serve as an indicator for better response from EGFR-TKI treatment.

Keywords: Epidermal growth factor receptor; Gene amplification; Lung adenocarcinoma; Mutation; Tumor heterogeneity; Tyrosine kinase inhibitor.