Abstract
BACKGROUND: We aimed to investigate the prevalence and prognostic role of Sex determining region Y-box 2 (SOX2) amplification and expression in surgically resected esophageal squamous cell carcinoma (ESCC). METHODS: We evaluated 450 ESCC samples using fluorescence in-situ hybridization and immunohistochemistry for SOX2 gene amplification and protein expression, respectively. The relationships of gene status with various clinicopathological characteristics and patient survival were statistically analyzed. RESULTS: SOX2 amplifications and chromosome 3 gain were observed in 4.4% and 12.9% of patients with ESCC. SOX2 amplification was associated with later clinical stage, and chromosome 3 gain was associated with earlier clinical stage (P=0.025). Low and high SOX2 expression were found in 28.9% and 24.7% of cases, respectively. SOX2 expression was significantly associated with gene copy number variation (P=0.007). SOX2 amplification was associated with a significantly shorter disease-free survival (DFS) or overall survival (OS). However, chromosome 3 gain was associated with a significantly longer DFS or OS (P<0.001). Multivariate analysis using the Cox proportional hazard model indicated that SOX2 amplification was an independently poorer prognostic factor (DFS, P<0.001, HR 2.638, 95% CI, 1.581-4.403; OS, P<0.001, HR 2.608, 95% CI, 1.562-4.355), along with pathology tumor-node-metastasis (pTNM) stage, whereas chromosome 3 gain was an independently better prognostic factor (DFS, P=0.003, HR 0.486, 95% CI, 0.300-0.789; OS, P=0.003, HR 0.474, 95% CI, 0.289-0.779) for ESCC. CONCLUSIONS: This is the first study wherein SOX2 amplification and chromosome 3 gain in a large cohort of ESCC were evaluated. SOX2 amplification is an independently poorer prognostic factor, whereas chromosome 3 gain is an independently favorable prognostic factor. Our results suggest that SOX2 amplification and chromosome 3 gain are potential biomarkers related to tumor progression and risk stratification in ESCC.