No major tumorigenic role for beta-catenin in serrated as opposed to conventional colorectal adenomas

Br J Cancer. 2003 Jul 7;89(1):152-7. doi: 10.1038/sj.bjc.6601070.

Abstract

Intracellular redistribution of beta-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early tumorigenic event in most colorectal tumours. In serrated adenoma (SA), a newly recognised subtype of colorectal adenoma, APC mutations are uncommon, and the contribution of beta-catenin to tumorigenesis remains unclear. We compared intracellular localisation of beta-catenin and presence of mutations in exon 3 of beta-catenin between 45 SAs, with 71 conventional adenomas (CADs), and eight carcinomas invading the submucosa (SCAs). Widespread or focal nuclear beta-catenin expression was demonstrated in 7% of SAs (three out of 45), 61% of CADs (43 out of 71), and 88% of SCAs (seven out of eight). Cytoplasmic immunostaining for beta-catenin was demonstrated in 16% of SAs (seven out of 45), 77% of CADs (55 out of 71), and 88% of SCAs (seven out of eight). No mutation in exon 3 of beta-catenin was found in SAs or SCAs, while 7% of CADs (five out of 71) had beta-catenin mutations. No nuclear or cytoplasmic expression of beta-catenin was observed in the hyperplastic or conventionally adenomatous epithelium of mixed-type SAs. These findings suggest that beta-catenin mutation is unlikely to contribute to the tumorigenesis in SA, and that intracellular localisation of beta-catenin may not be associated with an early event of the tumour progression in most SAs.

MeSH terms

  • Adenoma / genetics*
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins
  • Cell Transformation, Neoplastic*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / pharmacology*
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Fluid / chemistry
  • Male
  • Middle Aged
  • Signal Transduction
  • Trans-Activators / genetics*
  • Trans-Activators / pharmacology*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin