Comprehensive analysis of epidermal growth factor receptor gene status in lung adenocarcinoma

The epidermal growth factor receptor (EGFR) gene status including tyrosine kinase domain somatic mutations, increased copy number, and protein overexpression are reported to be associated with response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer. The purpose of this study was to elucidate the prevalence of activated EGFR gene and the association between mutation, copy number, and protein overexpression.

In a cohort of consecutive patients with lung adenocarcinoma, polymerase chain reaction and direct sequencing (n = 89) were conducted through exons 18 to 21. Fluorescence in situ hybridization (FISH) (n = 89) and single-nucleotide polymorphism (SNP) array 6.0 (n = 77) were used to detect the gene copy number. The protein expression of EGFR was detected by standard immunohistochemistry (IHC) (n = 89).

Fifty-nine (66.3%) patients harbored somatic mutations of EGFR in tyrosine kinase domain, 55.1% were positive by IHC and 44.9% were positive by FISH, and 66.2% showed gain of copy number according to SNP array 6.0. EGFR somatic mutations are more common in women, never smokers, and tumors with better differentiation. Increased copy number detected by both FISH and SNP array 6.0 analysis is significantly correlated with mutations of EGFR.

The EGFR somatic mutation rate is significantly higher in Chinese patients with lung adenocarcinoma than western countries. Nevertheless, we found comparable FISH and IHC-positive rates between different ethnics. Considering that FISH may be affected by tumor heterogeneity and other factors, SNP array 6.0 analysis is a good alternative method to detect EGFR copy number variations.