Association between epidermal growth factor receptor gene copy number and ERCC1, BRCA1 protein expression in Chinese patients with non-small cell lung cancer

Abstract

Mutation in epidermal growth factor receptor (EGFR) gene may predict response to chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation between EGFR gene copy status and protein levels of drug-resistant genes, such as excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1), remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH), and protein levels of platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%, respectively). Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02). Further association studies demonstrated that EGFR gene copy number status was not correlated with protein levels of ERCC1 or BRCA1; however, expression of ERCC1 was significantly associated with that of BRCA1 in this set of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein expression, but ERCC1 protein levels were significantly correlated to BRCA1 protein expression levels in tumor tissues from Chinese patients with NSCLC.