title: TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer.
abstract: 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 > or =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 > or =T3 bladder cancer, but it had prognostic significance within the chemoresistant subgroup.
authors.affiliation: Department of Urology, Royal Hallamshire Hospital, The Central Sheffield University Hospitals, Sheffield, United Kingdom. khaver@naseerqureshi.freeserve.co.uk
authors.forename: K N
authors.initials: KN
authors.lastname: Qureshi
authors.forename: T R
authors.initials: TR
authors.lastname: Griffiths
authors.forename: M C
authors.initials: MC
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Marsh
authors.forename: J T
authors.initials: JT
authors.lastname: Roberts
authors.forename: R R
authors.initials: RR
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Lunec
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D014747:Vinblastine; D002945:Cisplatin; D008727:Methotrexate