PROGNOSTIC VALUE OF BCL-2 ONCOPROTEIN EXPRESSION IN STAGE-II COLON-CARCINOMA

The bcl-2 proto-oncogene encodes a M(r) 25,000 protein that has been s hown to prevent apoptosis or programmed cell death, The bcl-2 protein is detectable in basal cells of normal colonic epithelium, and an alte red topographic distribution of this protein is found in colonic neopl asms, However, the clinical significance of abnormal bcl-2 expression in colon carcinomas remains unknown, We examined the prognostic value of the bcl-2 protein in TNM stage II colon carcinomas and its relation ship to DNA ploidy, cell proliferation indices, p53 expression, and cl inicopathological features, We analyzed 119 resected and otherwise unt reated, paraffin-embedded stage II colon carcinomas for bcl-2 and p53 protein expression using immunohistochemistry. DNA ploidy and prolifer ative index (% S-phase + % G(2)-M) were determined by flow cytometry, and tumor grade and vascular microinvasion were assessed on histologic al sections, Cytoplasmic expression of the bcl-2 protein was detected in 72 (66%) of 110 carcinomas, and a high level of expression was sign ificantly correlated with diploid DNA content (P = 0.02) and low proli ferative activity (P = 0.005), bcl-2 was not associated with nuclear p 53 expression, In a univariate analysis, a higher fraction of bcl-2-po sitive tumor cells was associated with better relapse-free survival (P = 0.02) and overall survival (P = 0.05) rates, Moreover, a high level of bcl-2 expression was an independent predictor of better relapse-fr ee survival (P = 0.04), but not overall survival (P = 0.14), after adj ustment for other variables, including proliferative index, DNA ploidy , and race, In conclusion, bcl-2 overexpression is associated with fav orable prognostic features and may predict clinical outcome in stage I I colon carcinomas.