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

Bcl-2 is known to inhibit apoptosis and is thought to play a role in colore ctal tumour development. Studies of the promoter region of bcl-2 have indic ated the presence of a p53 responsive element which downregulates bcl-2 exp ression, Since p53 is commonly mutated in colorectal cancers, but rarely in those tumours showing microsatellite instability (MSI), the aim of this st udy 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 classe s depending upon their levels of MSI. MSI-high tumours demonstrated instabi lity 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 tum ours was quantified independently by two pathologists and assigned to one o f five categories, with respect to the number of cells which showed positiv e staining: 0, up to 5%; 1, 6-25%; 2, 26-50%; 3, 51-75%; and 4, greater tha n or equal to 76%, Bcl-2 negative tumours were defined as those with a scor e of 0. Bcl-2 protein expression was tested for association with clinicopat hological stage, differentiation level, tumour site, age, sex, survival, ev idence of p53 inactivation and MSI level, A significant association was fou nd between bcl-2 expression and patient survival (P = 0.012, Gehan Wilcoxon test). Further, a significant reciprocal relationship was found between bc l-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.