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

BACKGROUND

We aimed to investigate the prevalence and prognostic role of () 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 gene amplification and protein expression, respectively. The relationships of gene status with various clinicopathological characteristics and patient survival were statistically analyzed.

RESULTS

amplifications and gain were observed in 4.4% and 12.9% of patients with ESCC. amplification was associated with later clinical stage, and 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). amplification was associated with a significantly shorter disease-free survival (DFS) or overall survival (OS). However, gain was associated with a significantly longer DFS or OS (P<0.001). Multivariate analysis using the Cox proportional hazard model indicated that 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 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 amplification and gain in a large cohort of ESCC were evaluated. amplification is an independently poorer prognostic factor, whereas gain is an independently favorable prognostic factor. Our results suggest that amplification and gain are potential biomarkers related to tumor progression and risk stratification in ESCC.