SOX2 amplification and chromosome 3 gain significantly impact prognosis in esophageal squamous cell carcinoma.

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.