Small tumor size and limited smoking history predicts activated epidermal growth factor receptor in early-stage non-small cell lung cancer.

Abstract

STUDY OBJECTIVE: Epidermal growth factor receptor (EGFR) signaling has been implicated in the pathogenesis of bronchial dysplasia and overt non-small cell lung cancer (NSCLC). We hypothesized that assaying for EGFR activity using an antibody that recognizes phosphorylated EGFR (pEGFR) may identify a subset of patients whose tumor cells are dependent on EGFR signaling. We also hypothesized that EGFR activity may be prognostic for early-stage NSCLC. DESIGN: We constructed high-density tissue microarrays using tissues from 193 surgically resected stage I NSCLCs. These arrays were immunostained with a pEGFR antibody, and the intensity of staining was correlated with clinicopathologic variables, as well as disease-free and overall survival (OS). Staining was scored by intensity and the percentage of positively stained tumor cells in triplicate. MEASUREMENTS AND RESULTS: We found the expression of pEGFR (with > 50% of tumor cells staining positive) in 51% of tumor tissues. We found an inverse correlation between pEGFR, and both tumor size and the degree of tobacco smoking. In addition, we found a trend in which pEGFR expression was inversely correlated with disease stage (IA higher than IB). There was no correlation with sex, histology, or disease-free or OS. CONCLUSIONS: Our results suggest that pEGFR levels are present in early-stage NSCLC, especially in patients with small tumors and in those with short smoking histories, but there is no prognostic impact on a patient's disease course. Targeting EGFR may therefore have more promise in chemoprevention or in patients with smaller early-stage NSCLCs compared with those with more advanced disease.