TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer

To examine retrospectively the prognostic significance of TP53 immunoreacti vity for both tumor response and patient survival in 83 patients with nonme tastatic muscle-invasive bladder cancer treated with a single transurethral resection (TUR) of tumor and combined cisplatin-based systemic chemotherap y followed by repeat TUR, paraffin-embedded sections of a bladder tumor obt ained at TUR before chemotherapy (1 T-2, 52 T-3, and 30 T-4) were immunosta ined for TP53 using monoclonal PAb1801 and DO-7 antibodies. For the entire cohort, TP53 immunopositivity (PAb1801 or DO-7) did not pred ict complete response (CR), complete or partial response (PR), progressive disease, or time to death from bladder cancer. There was a highly significa nt correlation between PAb1801 and DO-7 nuclear immunoreactivity (r = 0.824 2; P < 0.0001). In 76 patients in which complete clinical data were availab le, tumor stage (T-2/T-3; P = 0.0499), CR and PR (P = 0.0016) and CR (P < 0 .0001) were associated with patient survival. In a multivariate model, CR ( P < 0.0001) was the only independent predictor of improved survival. In com plete responders, neither TP53 immunostaining nor clinicopathological facto rs stratified patients into prognostic groups, However, in the subset of pa tients (n = 38) who were chemoresistant (PR or progressive disease), improv ed survival was associated with greater than or equal to 20% TP53 immunorea ctivity (PAb1801; P = 0.0191) and tumor stage (T-2/T-3; P = 0.0358), TP53 immunopositivity (PAb1801 or DO-7) did not predict overall survival or response to systemic chemotherapy in patients with nonmetastatic but predo minantly clinical stage greater than or equal to T-3 bladder cancer, but it had prognostic significance within the chemoresistant subgroup.