Expression of Bcl-2 protein is decreased in colorectal adenocarcinomas with microsatellite instability

Kelli G. Biden, Lisa A. Simms, Margaret Cummings, Ron Buttenshaw, Estelle Schoch, Jeffrey Searle, Glenda Gobe, Jeremy R. Jass, Stephen J. Meltzer, Barbara A. Leggett, Joanne Young

Research output: Contribution to journalArticlepeer-review

Abstract

Bcl-2 is known to inhibit apoptosis and is thought to play a role in colorectal tumour development. Studies of the promoter region of bcl-2 have indicated the presence of a p53 responsive element which downregulates bcl-2 expression. Since p53 is commonly mutated in colorectal cancers, but rarely in those tumours showing microsatellite instability (MSI), the aim of this study was to examine the relationship of bcl-2 protein expression to MSI, as well as to other clinicopathological and molecular variables, in colorectal adenocarcinomas. Expression of bcl-2 was analysed by immunohistochemistry in 71 colorectal cancers which had been previously assigned to three classes depending upon their levels of MSI. MSI-high tumours demonstrated instability in three or more of six microsatellite markers tested, MSI-low tumours in one or two of six, and MSI-null in none of six. Bcl-2 expression in tumours was quantified independently by two pathologists and assigned to one of five categories, with respect to the number of cells which showed positive staining: 0, up to 5%; 1, 6-25%; 2, 26-50%; 3, 51-75%; and 4, ≥ 76%. Bcl-2 negative tumours were defined as those with a score of 0. Bcl-2 protein expression was tested for association with clinicopathological stage, differentiation level, tumour site, age, sex, survival, evidence of p53 inactivation and MSI level. A significant association was found between bcl-2 expression and patient survival (P = 0.012, Gehan Wilcoxon test). Further, a significant reciprocal relationship was found between bcl-2 expression and the presence of MSI (P = 0.012, Wilcoxon rank sum test). We conclude that bcl-2 expressing colorectal cancers are more likely to be MSI-null, and to be associated with improved patient survival.

Original languageEnglish (US)
Pages (from-to)1245-1249
Number of pages5
JournalOncogene
Volume18
Issue number5
DOIs
StatePublished - Feb 4 1999

Keywords

  • Apoptosis
  • Bcl-2
  • Colorectal adenocarcinoma
  • Microsatellite instability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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