title: Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb.
abstract: Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10-67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13-52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01-7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24-69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours.
authors.affiliation: Department of Histopathology and Morbid Anatomy, Bart's & The London School of Medicine & Dentistry, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Hitchings
authors.forename: M
authors.initials: M
authors.lastname: Kumar
authors.forename: S
authors.initials: S
authors.lastname: Jordan
authors.forename: V
authors.initials: V
authors.lastname: Nargund
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000032:analysis*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53