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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)303-310
Number of pages8
JournalCellular Oncology
Volume32
Issue number4
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Colorectal cancer
  • Inflammatory bowel disease
  • P53
  • Surveillance
  • Wnt-pathway

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine

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