Relationship between EGFR gene copy number variation and EGFR mutations, protein expression, and clinicopathologic parameters in lung adenocarcinoma

Mutations of the epidermal growth factor receptor (EGFR) gene represent one type of genetic change in lung adenocarcinoma. Tyrosine kinase inhibitors are first line therapy for lung adenocarcinoma patients with EGFR mutations. EGFR gene copy number (GCN) variation is one screening tool for detecting EGFR mutations. However, the usefulness of EGFR GCNs is controversial. The aims of this study were to compare EGFR GCN, detected by single colored silver-enhanced in situ hybridization (SISH), with EGFR mutations, protein expression, and clinicopathologic parameters. Samples from 88 surgically resected lung adenocarcinoma patients were analyzed. EGFR protein expression was assessed by immunohistochemistry. EGFR GCN was examined by SISH. Scores of 5 (high polysomy) and 6 (amplification) were classified as EGFR SISH positive according to the Colorado scoring system. EGFR mutations were analyzed by direct deoxyribonucleic acid sequencing. The results showed that EGFR protein expression was present in 18.2% (16/88), EGFR SISH positivity in 20.5% (18/88), and EGFR mutations in 31.8% (28/88) of cases. EGFR SISH positivity was significantly correlated with EGFR protein expression (P<0.001). Results also showed that an increase in EGFR copy number (detected by SISH) was not significantly related to EGFR mutations. Therefore, EGFR SISH positivity cannot be used as a substitute for EGFR mutation analysis.