Overexpression of mutant EGFR protein indicates a better survival benefit from EGFR-TKI therapy in non-small cell lung cancer

Abstract

Background: Epidermal growth factor receptor (EGFR) is a novel target for therapy in a subset of non-small cell lung cancer (NSCLC). Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemistry (IHC) to detect EGFR L858R and del E746-A750 mutations in NSCLC patients and predict EGFR TKIs response. Methods: We collected specimens from 200 patients with NSCLC whose EGFR mutation status had been validated by direct DNA sequencing. IHC analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: The sensitivity, specificity, PPV, and NPV of IHC using EGFR del E746-A750 and L858R mutation antibodies were 95.0%/95.1%, 85.7%/94.1%, 74.0%/91.8%, and 97.6%/96.5%, respectively. When score 2+ and 3+ were considered as positive, the sensitivity, specificity, PPV, and NPV were 53.3%/36.6%, 99.3%/100%, 97.0%/100%, and 83.2%/65.3%, respectively. The median progression-free survival (PFS) after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (31.0 versus 13.0 months, p <0.05). Conclusions: IHC with EGFR mutation-specific antibodies is a promising screening method for detecting EGFR mutations in NSCLC patients. Otherwise, quantitative analysis of mutant EGFR expression might also predict the efficacy of TKIs treatment for NSCLC patients harboring sensitive EGFR mutation.