Wnt3a expression is associated with poor prognosis of esophageal squamous cell carcinoma.

Abstract

The Wnt signaling pathway is widely implicated in various types of cancer. Canonical Wnt signaling, including Wnt3a, may be a key component of cancer progression or chemoresistance. Consequently, it was hypothesized that Wnt3a expression may be a prognostic factor of esophageal squamous cell carcinoma (ESCC) due to its roles in chemoresistance and tumor progression. The aim of the present study was to investigate the association between Wnt3a expression and prognosis in patients with ESCC. Wnt3a expression was evaluated in resected specimens from 139 patients with thoracic ESCC who were subjected to curative surgery without neoadjuvant therapy in Tokai University Hospital between 2007 and 2009. Samples were assessed using immnohistochemistry. Patients with ESCC were divided into two groups according to the expression of Wnt3a in tumor tissue. The influence of Wnt3a expression on clinicopathological findings and prognosis of ESCC were subsequently investigated. Immnohistologically, 68 cases were Wnt3a-positive in the cytoplasm of cancer cells, whereas 71 cases were negative. Multivariate analysis by Cox proportional hazard model showed the association between pN (HR=3.539, P=0.001), venous invasion (HR=2.798, P=0.012), Wnt3a expression (HR=1.691, P=0.046) and overall survival (OS). OS rate and disease-free survival rate were poorer in Wnt3a-positive group compared with those in the Wnt3a-negative group as indicated by the log-rank test (P=0.012 and P=0.023, respectively). In pathological stages I and II, there was no significant difference in the OS rate between Wnt3a-positive and Wnt3a-negative groups; however, the OS rate of the Wnt3a-positive group was significantly worse than that of Wnt3a-negative group in pathological stage III (log rank test; P=0.017). Wnt3a-positive patients with recurrence had a significantly poorer prognosis compared with Wnt3a-negative patients (log-rank test; P=0.023). The present findings suggested that Wnt3a may be a prognostic factor of ESCC.