Positive Transforming Growth Factor-β Activated Kinase-1 Expression Has an Unfavorable Impact on Survival in T3N1-3M0 Esophageal Squamous Cell Carcinomas

Abstract

Transforming growth factor-β activated kinase-1 (TAK1) is a serine/threonine kinase in the mitogen-activated protein kinase kinase family. Previous studies have reported the role of TAK1 in cancer occurrence and progression; however, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been elucidated. We investigated the correlation of TAK1 expression and clinical outcome in T3N1-3M0 surgically resected ESCCs. Tissue microarrays constructed of 234 surgically resected T3N1-3M0 ESCC primary tumors were used for TAK1 evaluation by immunohistochemistry. The clinical and prognostic significance of TAK1 expression was analyzed statistically. Positive expression of TAK1 was observed in 38.5% (90 of 234). The expression level of TAK1 in ESCCs at stage N2-3 was significantly higher than the expression level in those at stage N1 (p = 0.041). Patients with negative TAK1 expression demonstrated better overall survival than those with positive expression (median, 22.7 vs 17.4 months; p = 0.023). Multivariate analysis showed that TAK1 expression was an independent prognostic factor in ESCC (relative risk, 1.429; p = 0.021). TAK1 expression correlates with lymph node metastasis and is a negative, independent prognostic factor in resected T3N1-3M0 ESCCs.