WNT-pathway activation in IBD-associated colorectal carcinogenesis: potential biomarkers for colonic surveillance

• Published in: Cellular oncology : the official journal of the International Society for Cellular Oncology 2010-01, Vol.32 (4), p.303-310
• Main Authors: Claessen, Marian M H, Schipper, Marguerite E I, Oldenburg, Bas, Siersema, Peter D, Offerhaus, G Johan A, Vleggaar, Frank P
• Format: Article
• Language: English
• Subjects: Adult; beta Catenin - genetics; beta Catenin - metabolism; Biomarkers, Tumor - metabolism; Carcinoma - complications; Carcinoma - diagnosis; Carcinoma - physiopathology; Colitis; Colon - metabolism; Colon - pathology; Colorectal Neoplasms - complications; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - physiopathology; Cyclin D1 - genetics; Cyclin D1 - metabolism; Disease Progression; DNA Mutational Analysis; Female; Genes, p53 - genetics; Humans; Immunohistochemistry; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - diagnosis; Inflammatory Bowel Diseases - physiopathology; Male; Microarray Analysis; Middle Aged; Signal Transduction; Wnt Proteins - metabolism
• ISSN: 1570-5870; 1875-8606
• DOI: 10.3233/CLO-2009-0503

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. 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 beta-catenin, cyclin D1 and p53. p53 sequence analysis was performed in some cases. Nuclear beta-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%). 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 beta-catenin may facilitate detection of neoplasia.