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

Lookup NU author(s): Dr Khaver Qureshi, Thomas Griffiths, Dr Mary Robinson, Dr James Roberts, Professor John LunecORCiD, Professor David Neal


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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.

Publication metadata

Author(s): Qureshi, K., Griffiths, T., Robinson, M., Marsh, C., Roberts, J., Hall, R., Lunec, J., Neal, D.E.

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 1999

Volume: 5

Issue: 11

Pages: 3500-3507

Print publication date: 01/11/1999

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

PubMed id: 10589764