P53 STATUS DOES NOT PREDICT INITIAL CLINICAL-RESPONSE TO BACILLUS-CALMETTE-GUERIN INTRAVESICAL THERAPY IN T1 BLADDER-TUMORS

Purpose: In superficial urothelial tumors of the bladder, p53 status i s currently the most informative pretreatment parameter to define a po pulation at higher risk for invasive carcinoma. Also, in T1 tumors, oc currence of muscular invasion is often related to an early relapse fol lowing BCG therapy. With the knowledge of biological parameters able t o identify the group of initial BCG therapy non-responders, it would b e possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the pred ictive value of the p53 tumor status on the early BCG therapy response . Materials and Methods: The population included a selected group of 4 3 patients presenting T1 bladder tumors with no carcinoma in situ (Tis ), treated by transurethral resection (TUR) followed by intravesical B CG therapy. Clinical outcome was analyzed in relation to usual clinica l and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using D07 monoclonal a ntibody. For 16 specimens, p53 gene was investigated using a Single St rand Conformation Polymorphism (SSCP) analysis and sequence determinat ion. Results: p53 anomalies were strongly correlated to smoking behavi or (p=0.003) and tumoral grade (p=0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followu p revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of D07 immunostaining in det ection of p53 anomalies. Conclusions: In T1 bladder tumors, pretreatme nt p53 determination was not useful to define a group of early BCG non -responders. Thus, p53 status and immunological response induced by BC G endovesical therapy are two independent events.