High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas

BACKGROUND: SOX2 is an embryonic developmental transcription factor, which is important in the development of the respiratory tract. SOX2 overexpression is associated with aggressive disease in several tumor types. However, SOX2 overexpression and gene amplification associates with favorable outcome in lung squamous cell carcinomas (SCC) and dissimilar results have been reported in lung adenocarcinomas (ADC). The aim of the present study was to evaluate SOX2 expression in NSCLC and determine the relationship with clinico-pathological variables and outcome. METHODS: SOX2 protein levels were measured in tissue microarrays (TMAs) containing FFPE samples from two independent lung cancer cohorts (n = 340 & 307) using automated quantitative immunofluorescence (QIF). Assay validation was performed using FFPE preparations of cell lines with known SOX2 expression. Associations of SOX2 levels with main clinico-pathological characteristics and with overall survival were studied using uni-and multivariate analysis. RESULTS: SOX2 levels were higher in patients with SCC than in ADC in both cohorts (p value<0.0001). In the training cohort, NSCLC patients whose tumors showed high SOX2 (n = 245) had longer survival than those with low SOX2 levels (log rank p = 0.0002). Comparable results were observed in the second independent validation cohort, log rank p = 0.0113. SOX2 positive cases showed a 58% reduction in risk of death in Cox univariate analysis (hazards ratio-HR = 0.42 confidence interval-CI (0.36,0.73), p = 0.0002). SOX2 was associated with significantly longer survival independent of histology in multivariate analysis (hazards ratio-HR = 0.429 confidence interval-CI (0.295, 0.663), p = <0.001). CONCLUSIONS: SOX2 is an independent positive prognostic marker in NSCLC. Increased SOX2 levels are more frequent in SCC than in ADC, but the association with better survival is independent from the histological subtype.