Aberrant Wnt1/β-Catenin Expression is an Independent Poor Prognostic Marker of Non-small Cell Lung Cancer After Surgery

Abstract

The Wnt signaling pathway plays a major role in cancer development and progression. As a novel anticancer drug can be developed using inhibitors of this pathway, we investigated the clinical significance of the Wnt signaling pathway molecules in non-small cell lung cancer (NSCLC). Immunohistochemical analysis of a tissue microarray with 262 resected NSCLC specimens was performed to study the expression and subcellular localization of Wnt1 in relation to downstream molecules, including GSK-3β, β-catenin, c-Myc, cyclin D1, and p53. These results were correlated with other clinicopathologic features. Cytoplasmic Wnt1 overexpression was detected in 36.6% (96 of 262) NSCLCs, and aberrant β-catenin staining was identified in 76% (189 of 262) of NSCLCs. There were significant associations between Wnt1 expression and altered expression of β-catenin (p = 0.034), overexpression of c-Myc (p < 0.001), or overexpression of cyclin D1 (p = 0.018). While there was no significant association between Wnt1 or β-catenin and stage, the 5-year survival was significantly lower in patients with Wnt1- and β-catenin-positive NSCLCs than negative NSCLCs (p < 0.05, respectively). In multivariate analysis, stage and Wnt1+/β-catenin+ expression were independent prognostic factors of overall survival (p < 0.05). These findings show that Wnt1 expression may be one of the possible mechanisms of the activation of the canonical Wnt/β-catenin signaling pathway in NSCLC, and Wnt1 and altered β-catenin expression are poor prognostic markers, independent of stage.