IMMUNOHISTOCHEMICALLY DETECTABLE BCL-2 EXPRESSION IN COLORECTAL-CARCINOMA - CORRELATION WITH TUMOR STAGE AND PATIENT SURVIVAL

The bcl-2 gene encodes for a mitochondrial membrane proto-oncoprotein, the expression of which is known to suppress programmed cell death (a poptosis). In the present study the prognostic value of bcl-2 proto-on coprotein was immunohistochemically investigated in a series of 104 co lorectal carcinomas. The bcl-2 staining patterns were semiquantitative ly assessed and correlated with the pTNM stage, Dukes' classification, lymphocytic infiltration (Jass classification) and tumour grade as we ll as parameters not associated with prognosis (gender, age, tumour si te, histological tumour type). Statistical analysis was carried out us ing the Kaplan-Meier method, the log-rank test, hazard ratios and thei r confidence intervals. Fifty-five out of 104 cases completely lacked immunohistochemical bcl-2 expression. Fewer than 5% of bcl-2-positive cells were found in 25, 5-50% in 17 and more than 50% in five cases. T he extent of bcl-2 expression by tumour cells decreased significantly with respect to increasing tumour size (P<0.05), decreasing lymphocyti c infiltration (P<0.05) and chance of poor clinical outcome (P<0.05), but not with worsening of Dukes stages. In multivariate analysis (Cox regression model) bcl-2 expression remained as an independent prognost ic parameter with Dukes' classification as stratification factor (P<0. 001). Although the biological functions of bcl-2 protein are not yet w ell understood, our results provide further evidence that bcl-2 Oncopr otein appears to be associated with favourable clinical outcome. Thus immunohistochemical bcl-2 phenotyping of colorectal carcinoma may cont ribute in future to the clinical management of these patients.