RECIPROCAL EXPRESSION OF BCL-2 AND P53 ONCOPROTEINS IN UROTHELIAL DYSPLASIA AND CARCINOMA OF THE URINARY-BLADDER

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohisto chemically in matched normal urothelium, dysplasia and cancer specimen s selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartmen t, while in moderate and severe dysplasia its expression was detectabl e also in the upper regions. Excess bcl-2 immunoreactivity was found i n 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs s howed bcl-2 expression compared with that of low-grade TCCs (P < 0.05) . Overexpression of p53 protein showed a increasing trend toward the p rogression of bladder tumorigenesis (P < 0.01) and a significant recip rocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolu tion from mild dysplasia to carcinoma in individual cases, loss of bcl -2 expression was more frequently observed in superficial (P < 0.02) o r low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for bot h bcl-2 and p53 in cancer lesions had a significantly more favorable p rognosis compared with those with positive immunostaining for the onco proteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earl ier than p53, appears to facilitate bladder tumorigenesis and to enhan ce tumor aggression in some extent.