Activation state egfr and STAT-3 as prognostic markers in resected non-small cell lung cancer

Background: Total EGFR expression by immunohistochemistry (IHC) has failed to demonstrate prognostic importance. We hypothesized that activation (phosphorylated) state of EGFR (p-EGFR) and its activated downstream signal pathway (p-STAT-3) wilt have prognostic value in NSCLC. Methods: 145 patients underwent lung resection for NSCLC at University Hospitals from 1998-2002. A database with TNM stage, gender, age, time to recurrence, and survival was established. p-EGFR and p-STAT-3 levels were quantified by IHC. Specimens were divided into negative, 1+, 2+, or 3+ (5-19%, 20-50%7 > 50% of tumor cells staining respectively). Cox pro-portional hazard model was used for multivariate analysis. Results: Median age was 70 years. 58% were female and 54% had adenocarcinoma. Pathologic stage was as follows: stage 1: 54%, stage It: 31%, stage 111: 15%. 32% were positive for p-EGFR (squamous 36%, adenocarcinoma 29%). p-STAT-3 staining was seen in 38% and was higher in adenocarcinoma (46%) versus squamous cell (27%, p = 0.02) and was higher in patients > 70 years than compared to those < 70 years (p = 0.06). There was a trend toward co-expression of p-EGFR and p-STAT-3 (p = 0.09). The 5-year Kaplan-Meier probabilities of overall survival were not different amongst patients with activated versus no activation of EGFR and STAT-3. Conclusions: Although EGFR is commonly expressed in NSCLC (similar to 70%), p-EGFR is seen in only 1/3 of patients. p-EGFR and p-STAT-3 were commonly co-expressed in tumors compatible with known signal transduction pathways in lung cancer. However, EGFR and STAT-3 activation status does not provide prognostic information in resected disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved.