P53 AND RB EXPRESSION PREDICT PROGRESSION IN T-1 BLADDER-CANCER

The optimal clinical management of minimally invasive (stage T-1) blad der cancer is controversial, T-1 bladder cancers share characteristics of both noninvasive (T-a) papillary cancer and high stage, muscle-inv asive bladder cancers, Patients with T-1 bladder cancer have a higher risk of cancer progression and death than do patients with T-a bladder cancer, However, this risk is much lower than that of patients with h igh-stage bladder cancers, Methods of identifying T-1 bladder cancer p atients at greatest risk for progression may significantly improve cli nical management, We retrospectively evaluated two tumor suppressor ge nes, p53 and RE, as potential prognostic markers for progression in a cohort of 45 patients with pT(1) bladder cancer, Median follow-up for these individuals was greater than 3.5 years, Of this group, 58% had a ltered p53 expression based on positive p53 immunostaining, Three patt erns for RE nuclear protein staining were observed: absent, heterogene ous (normal), and strongly homogeneous, Progression-free survival was similar for patients with loss of RE protein expression and those with apparent overexpression of RE protein, Therefore, both staining patte rns were considered abnormal, Patients with normal expression of both proteins (ie., p53 negative and RE heterogeneously positive) had an ex cellent outcome, with no patient showing disease progression, whereas patients with abnormal expression of either or both proteins had a sig nificant increase in progression (P = 0.04 and P = 0.005, respectively ), These data support the stratification of T-1 bladder cancer patient s based on p53 and RE nuclear protein status and suggest that patients with normal protein expression for both genes can be managed conserva tively, whereas patients with alterations in one and particularly both genes require more aggressive treatment.