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

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, > or =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.

• Authors: K G Biden, L A Simms, M Cummings, R Buttenshaw, E Schoch, J Searle, G Gobe, J R Jass, S J Meltzer, B A Leggett, J Young
• Journal: Oncogene (Oncogene) Vol. 18 Issue 5 Pg. 1245-9 (Feb 04 1999) ISSN: 0950-9232 [Print] England
• PMID: 10022131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proto-Oncogene Proteins c-bcl-2

Topics

• Adenocarcinoma (genetics, mortality)
• Age Factors
• Apoptosis
• Cohort Studies
• Colorectal Neoplasms (genetics, mortality)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, p53
• Humans
• Immunohistochemistry
• Male
• Proto-Oncogene Proteins c-bcl-2 (isolation & purification)
• Sex Factors
• Trinucleotide Repeat Expansion