Overexpression of SOX2 Is Associated with Better Overall Survival in Squamous Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy

Abstract

PURPOSE: The purpose of this study is to investigate the prognostic significance of SOX2 gene amplification and expression in patients with American Joint Committee on Cancer stage III lung squamous cell carcinoma (SCC) who underwent surgery followed by adjuvant radiotherapy. MATERIALS AND METHODS: Pathological specimens were obtained from 33 patients with stage III lung SCC treated with surgery followed by adjuvant radiotherapy between 1996 and 2008. SOX2 gene amplification and protein expression were analyzed using fluorescent in situ hybridization and immunohistochemistry, respectively. Patients were divided into two groups according to their SOX2 gene amplification and protein expression status. Kaplan-Meier estimates and a Cox proportional hazards model were used to identify the prognostic factors affecting patient survival. RESULTS: The median follow-up period for surviving patients was 58 months (range, 5 to 102 months). SOX2 gene amplification was observed in 22 patients and protein overexpression in 26 patients. SOX2 overexpression showed significant association with SOX2 gene amplification (p=0.002). In multivariate analysis, SOX2 overexpression was a significant prognostic factor for overall survival (OS) (hazard ratios [HR], 0.1; 95% confidence interval [CI], 0.002 to 0.5; p=0.005) and disease-free survival (DFS) (HR, 0.15; 95% CI, 0.04 to 0.65; p=0.01). Age (HR, 0.33; 95% CI, 0.11 to 0.98; p=0.046) and total radiation dose (HR, 0.13; 95% CI, 0.02 to 0.7; p=0.02) were the independent prognostic factors for OS and DFS. Patients with SOX2 amplification did not show a longer OS (p=0.95) and DFS (p=0.48). CONCLUSION: Our data suggested that SOX2 overexpression could be used as a positive prognostic factor in patients with stage III lung SCC receiving adjuvant radiotherapy.