High Coexpression of Both EGFR and IGF1R Correlates With Poor Patient Prognosis in Resected Non-Small-Cell Lung Cancer

The expression profiles of the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) were determined by immunohistochemical (IHC) analysis (n = 184) and Western blot analysis (n = 40) in patients with nonesmall-cell lung cancer (NSCLC) who had undergone surgical resection. High coexpression of both receptors (H-score >= 200) was more common in squamous cell carcinoma (SCC) and correlated with poor overall survival (OS) (P = .04). This subset of patients may respond favorably to combination targeted therapies. Background: Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected nonesmall-cell lung cancer (NSCLC). Methods: EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. Results: High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P = .028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P = .0004). A significant association was shown between EGFR and IGF1R protein overexpression (P < .005). Patients with high expression of both receptors had a poorer overall survival (OS) (P = .04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P = .0004 and P = .0009), with SCC having higher expression levels than ADC. Conclusion: Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. (C) 2014 Elsevier Inc. All rights reserved.