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

Cell Oncol. 2010 Jan 1;32(4):303-10. doi: 10.3233/CLO-2009-0503.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • 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*
  • DNA Mutational Analysis
  • Disease Progression
  • 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
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1