ß-Catenin and its relation to VEGF and cyclin D1 expression in pT3 rectosigmoid cancers

Abstract

BACKGROUND/AIMS: β-Catenin is a critical component of the Wnt signaling pathway that regulates cell proliferation and differentiation. Wnt signaling leads to the stabilization of cytosolic β-catenin and to translocation to the nucleus, where it binds with T-cell factor and promotes the transcription and changes in target gene expression, including vascular endothelial growth factor and cyclin D1. The aim of this study was to assess the expression of cyclin D1 and vascular endothelial growth factor and to correlate them with β-catenin expression and some clinicopathologic parameters. METHODS: In this study, we analyzed paraffin-embedded specimens from 42 patients with pT3 rectosigmoid cancer for β-catenin, vascular endothelial growth factor and cyclin D1 expression using immunohistochemistry. RESULTS: Thirty-six (85.7%) and 24 (57.1%) tumors expressed vascular endothelial growth factor and cyclin D1, respectively. Nuclear expression of β-catenin was detected in only 26.1% of tumors. It was revealed that cytoplasmic β-catenin expression was significantly related to vascular endothelial growth factor expression (p=0.011). No association was found between nuclear or cytoplasmic β-catenin and cyclin D1 expression. No significant association was seen between β-catenin, vascular endothelial growth factor or cyclin D1 expression and some investigated clinicopathologic features. CONCLUSIONS: Our results may contribute to knowledge regarding the functional interaction between β-catenin and vascular endothelial growth factor. We suggest that the overexpression of cyclin D1 in rectosigmoid cancers may be more complicated than purely upregulation by β-catenin. Further larger studies on Wnt/β-catenin and target gene activity and protein expression are necessary to better understand and define their roles in the pathogenesis of colorectal carcinoma.