Relationship between epidermal growth factor receptor gene mutation and copy number in Chinese patients with non-small cell lung cancer

Abstract

Epidermal growth factor receptor (EGFR) gene mutation and copy number are useful predictive markers that guide the selection of non-small cell lung cancer (NSCLC) patients for EGFR-targeting therapy. This study aimed to investigate the correlation between EGFR gene mutation and copy number and clinicopathologic characteristics of Chinese patients with NSCLC. NSCLC specimens collected from 205 patients between November 2009 and January 2011 were selected to detect EGFR gene mutations with real-time polymerase chain reaction (RT-PCR) and to detect EGFR gene copy number with fluorescence in situ hybridization (FISH). EGFR mutations primarily occurred in females, non-smokers, and patients with adenocarinomas (all P < 0.001). Tissues from 128 (62%) patients were FISH-positive for EGFR, including 37 (18%) with gene amplification and 91 (44%) with high polysomy. EGFR gene mutation was correlated with FISH-positive status (R = 0.340, P < 0.001). Multivariate analysis showed that not smoking (OR = 5.910, 95% CI = 2.363-14.779, P < 0.001) and having adenocarcinoma (OR = 0.122, 95% CI = 0.026-0.581, P = 0.008) were favorable factors for EGFR gene mutation. These results show a high frequency of EGFR FISH positivity in NSCLC tissues from Chinese patients and a significant relevance between EGFR gene mutations and FISH-positive status. Among the FISH-positive samples, EGFR gene mutation occurred more frequently in samples with gene amplification compared to those with high polysomy, suggesting that EGFR mutation and gene amplification should be used as clinical decision parameters to predict response to EGFR-targeting therapy.

Figure 1.. Representative real-time polymerase chain reaction (RT-PCR) curves for mutations in EGFR exons 19 and 21.

The positive control curve shows the mutation. Two ascending curves denoted “positive sample” represent exon 19 delE746-A750 mutation (A) and exon 21 L858R mutation (B). Smooth curves represent wild-type EGFR.

Figure 2.. EGFR gene copy number analyzed with fluorescence in situ hybridization (FISH).

Chromosome 7 centromere was labeled with FITC (green) and EGFR gene was labeled with rhodamine (red). A, EGFR high polysomy; B, EGFR amplification; C, EGFR disomy; D, EGFR low polysomy; E, EGFR low trisomy; F, EGFR high trisomy.