β-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis

Xingpei Hao, Ian M. Frayling, Teresa C. Willcocks, Wei Han, Ian P. Tomlinson, Massimo N. Pignatelli, Theresa P. Pretlow, Ian C. Talbot

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20 Citations (Scopus)

Abstract

β-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of β-catenin, while 46% of adenomas and 79% of carcinomas displayed β-catenin nuclear expression. Importantly, a reciprocal relationship between reduced membranous and increased nuclear β-catenin expression was demonstrated in the development from adenoma to carcinoma. To clarify whether this relates to an abnormality of the APC gene (APC), we have now studied allele loss in microdissected tissues from 74 adenomas and 21 carcinomas (sporadic cases, previously immunostained for β-catenin) by analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors (57.8%) showed allele loss at APC (no difference between adenomas and carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased nuclear localization and reduced membranous staining of β-catenin, and thirteen tumors (13/55, 23.6%) manifested either nuclear expression without changes in membranous expression or reduced membranous staining without nuclear expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved normal membranous expression. Adenomas and carcinomas showing both nuclear and reduced membranous expression of β-catenin, compared with those with normal membranous expression, tended to show allele loss (P<0.01). In addition, 24 (24/95, 25.6%) tumors showed a change in the pattern of β-catenin expression, but did not exhibit allele loss. These results suggest that although there may be a number of mechanisms responsible for changes in β-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon.

Original languageEnglish
Pages (from-to)362-366
Number of pages5
JournalVirchows Archiv
Volume440
Issue number4
DOIs
Publication statusPublished - Apr 27 2002

Keywords

  • APC
  • Adenoma
  • Allele loss
  • Carcinoma
  • Colorectum
  • β-catenin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hao, X., Frayling, I. M., Willcocks, T. C., Han, W., Tomlinson, I. P., Pignatelli, M. N., Pretlow, T. P., & Talbot, I. C. (2002). β-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. Virchows Archiv, 440(4), 362-366. https://doi.org/10.1007/s00428-001-0570-0