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TP53 Accumulation Predicts Improved Survival in Patients Resistant to Systemic Cisplatin-based Chemotherapy forMuscle-invasive Bladder Cancer¹

Department of Urology, Royal Hallamshire Hospital, The Central Sheffield University Hospitals, Sheffield, United Kingdom S10 2JF [K. N. Q.]; Department of Surgery [T. R. L. G., D. E. N.] and Cancer Research Unit [J. L.], The Medical School, University of Newcastle, Newcastle-upon-Tyne, United Kingdom NE2 4HH; Department of Pathology [M. C. R., C. M.] and Northern Cancer Network [R. R. H.], Freeman Hospital, Newcastle-upon-Tyne, United Kingdom NE7 7DN; and Northern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle-upon-Tyne, United Kingdom NE4 6BE [J. T. R.]

To examine retrospectively the prognostic significance of TP53 immunoreactivity for both tumor response and patient survival in 83 patients with nonmetastatic muscle-invasive bladder cancer treated with a single transurethral resection (TUR) of tumor and combined cisplatin-based systemic chemotherapy followed by repeat TUR, paraffin-embedded sections of a bladder tumor obtained at TUR before chemotherapy (1 T₂, 52 T₃, and 30 T₄) were immunostained for TP53 using monoclonal PAb1801 and DO-7 antibodies.

For the entire cohort, TP53 immunopositivity (PAb1801 or DO-7) did not predict complete response (CR), complete or partial response (PR), progressive disease, or time to death from bladder cancer. There was a highly significant correlation between PAb1801 and DO-7 nuclear immunoreactivity (r = 0.8242; P < 0.0001). In 76 patients in which complete clinical data were available, tumor stage (T₂/T₃; 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 complete responders, neither TP53 immunostaining nor clinicopathological factors stratified patients into prognostic groups. However, in the subset of patients (n = 38) who were chemoresistant (PR or progressive disease), improved survival was associated with 20% TP53 immunoreactivity (PAb1801; P = 0.0191) and tumor stage (T₂/T₃; P = 0.0358).

TP53 immunopositivity (PAb1801 or DO-7) did not predict overall survival or response to systemic chemotherapy in patients with nonmetastatic but predominantly clinical stage T₃ bladder cancer, but it had prognostic significance within the chemoresistant subgroup.

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