Literature DB >> 20208143

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

Marian M H Claessen1, Marguerite E I Schipper, Bas Oldenburg, Peter D Siersema, G Johan A Offerhaus, Frank P Vleggaar.   

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

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Year:  2010        PMID: 20208143      PMCID: PMC4619233          DOI: 10.3233/CLO-2009-0503

Source DB:  PubMed          Journal:  Cell Oncol        ISSN: 1570-5870            Impact factor:   6.730


  30 in total

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