AIM:To assess whether differential expression of caspase-3 in paired metastatic lymph nodes(LNs)is prognostic of survival in patients with resectable esophageal squamous cell carcinoma(ESCC).METHODS:Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays.The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.RESULTS:The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors(P<0.001).Caspase-3 expression in the primary tumors was associated with longer median survival(23 mo vs21 mo,P=0.033),whereas higher expression in paired metastatic LNs was associated with shorter median survival(20 mo vs 22 mo,P=0.043).Multivariate analysis showed that both were independent prognostic factors.CONCLUSION:Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis.Protein expression in metastatic tumors may be a biomarker prognostic of survival.