WNT-Pathway Activation in IBD-Associated Colorectal Carcinogenesis: Potential Biomarkers for Colonic Surveillance

Abstract

Objectives : The Wnt-pathway dominates the sporadic carcinogenesis whereas p53 plays a pivotal role in the colitis-associated counterpart. The expression of Wnt-signaling proteins and p53 during colitis-associated carcinogenesis was determined. Methods : A tissue microarray was constructed with colonic samples from 5 groups of patients: controls (C, n =10), IBD without neoplasia (IBD, n =12), non-dysplastic IBD with neoplasia elsewhere in the colon (IBD-NE, n =12), dysplastic lesion in IBD (IBD-DYS, n =12), and IBD-associated colorectal cancer (IBD-CRC, n =10). Immunohistochemistry was performed for β -catenin, cyclin D1 and p53. p53 sequence analysis was performed in some cases. Results : Nuclear β -catenin expression was found in 0%, 0%, 50%, 55% and 100% of the patients in the C-, IBD-, IBD-NE-, IBD-DYS- and IBD-CRC-groups, respectively. Non-dysplastic IBD mucosa with neoplasia detected elsewhere showed nuclear expression in 50% of the cases compared to 0% in IBD mucosa without neoplasia ( p =0.02). Cyclin D1 staining had similar expression patterns. Overexpression of p53 was only detected in the IBD-DYS (66.7%) and IBD-CRC groups (50%). Conclusion : In contrast to previous findings, our results suggest activation of the Wnt-pathway in the early phase of colitis-associated carcinogenesis. Furthermore, as Wnt activation was observed in 50% of the IBD-NE cases, nuclear β -catenin may facilitate detection of neoplasia.