EXPRESSION OF BCL-2 AND BCL-X IN BLADDER-CANCER

Purpose: TP53 and RBI gene mutations in bladder transitional cell carc inoma (TCC) are correlated with grade, stage, recurrence, and survival and may correlate with tumor cell apoptotic potential. Overexpression of the bcl-2 and bcl-X anti-apoptotic genes has been correlated with poor prognosis and chemotherapy resistance in other systems. Similar s tudies have not been performed in TCC. We thus sought to determine exp ression of bcl-2 and bcl-X in TCC and correlate these with stage, surv ival and abnormal pRb or p53 expression. Materials and Methods: Forty- two TCC samples (19 Ta and 23 locally advanced tumors) and normal urot helial controls were examined. Immunohistochemistry for p53, pRb, bcl- 2 and bcl-X was performed on an automated system using indirect strept avidin biotin/horseradish peroxidase staining. Western immunoblot anal ysis was performed on bladder cancer cell lines to further characteriz e bcl-X expression. Recurrence-free and disease-specific survival were retrospectively determined. Kaplan-Meier survival curves were compare d using the log rank test, and correlation of abnormal staining with s tage and p53 or pRb status was determined using Fisher's exact test. R esults: Bcl-2 was expressed in less than 1% of normal urothelial cells , but moderate expression of bcl-x was found in all normal urothelial samples. Only 7.0% of TCC samples (1/19 Ta and 2/23 locally advanced t umors) demonstrated bcl-2 overexpression. Bcl-X overexpression was obs erved in 45.2% of TCC (8/19 Ta and 11/23 locally advanced tumors). Wes tern blot analysis also revealed that both the long (29 kDa) anti-apop totic form and short (19 kDa) pro-apoptotic form were overexpressed in bladder cancer cell lines and normal human urothelial cells. Bcl-X ov erexpression was weakly correlated with normal p53 expression (p = 0.0 6). There were no correlations of bcl-2 and bcl-X overexpression with abnormal p53, pRb, or tumor stage. There were no differences in recurr ence-free or overall survival in patients with abnormal bcl-X staining . Conclusions: Bcl-2 overexpression is rare in TCC. Bcl-X overexpressi on is common, likely reflecting its expression pattern in normal uroth elium, but is not correlated with stage or abnormal p53 or pRb stainin g. Within the power Limitations of this small study, bcl-X overexpress ion is not correlated with recurrence or survival.