Predictive Value of Cell Cycle Biomarkers in Nonmuscle Invasive Bladder Transitional Cell Carcinoma

No AccessJournal of UrologyAdult urology1 Feb 2007Predictive Value of Cell Cycle Biomarkers in Nonmuscle Invasive Bladder Transitional Cell Carcinoma Shahrokh F. Shariat, Raheela Ashfaq, Arthur I. Sagalowsky, and Yair Lotan Shahrokh F. ShariatShahrokh F. Shariat Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. Supported by the Austrian Program for Advanced Research and Technology. More articles by this author , Raheela AshfaqRaheela Ashfaq Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. More articles by this author , Arthur I. SagalowskyArthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. More articles by this author , and Yair LotanYair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with Matritech Inc. and Boehringer Ingelheim. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2006.09.038AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We determined whether the combined expression of p53, p21, p27 and pRB is associated with outcomes of patients with nonmuscle invasive bladder transitional cell carcinoma. Materials and Methods: Immunohistochemical staining for p53, p21, p27 and pRB was performed on archival bladder specimens from 9 normal controls and 74 patients who underwent transurethral bladder tumor resection for Ta, Tis and/or T1 transitional cell carcinoma. Results: Normal urothelium had wild type status of p53, pRB, p21 and p27. p53 expression was altered in 34% of patients with transitional cell carcinoma, pRB in 39%, p21 in 35% and p27 in 47%. When analyzed separately, p53, pRB and p21 were each independently associated with tumor progression. Combination of biomarkers stratified patients into statistically significantly different risk groups for disease recurrence and progression. When tumor stage and grade were modeled with all 4 biomarkers, p53 and p27 were the sole independent predictors of disease recurrence and progression. After controlling for the effects of tumor grade and stage, the incremental number of altered biomarkers was associated with an increased risk of bladder cancer recurrence (p for trend = 0.011) and progression (p for trend = 0.005). The risk ratio for disease recurrence and progression increased incrementally with the number of biomarkers altered. Conclusions: Combinations of p53, pRB, p21 and p27 had cooperative/synergistic effects stratifying patients into different risk groups. Higher total numbers of altered biomarkers were independently associated with an increased risk of disease progression and death. Prospective trials are necessary to usher bladder cancer management into the age of molecular biomarkers. References 1 : Superficial bladder cancer: progression and recurrence. J Urol1983; 130: 1083. Abstract, Google Scholar 2 : Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol2000; 163: 1124. Link, Google Scholar 3 : The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts. Embo J1999; 18: 1571. Google Scholar 4 : Correlation of immunohistochemical molecular staging of bladder biopsies and radical cystectomy specimens. 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Google Scholar © 2007 by American Urological AssociationFiguresReferencesRelatedDetailsCited byGayed B, Youssef R, Bagrodia A, Kapur P, Darwish O, Krabbe L, Sagalowsky A, Lotan Y and Margulis V (2018) Prognostic Role of Cell Cycle and Proliferative Biomarkers in Patients with Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 190, NO. 5, (1662-1667), Online publication date: 1-Nov-2013.Shariat S, Chade D, Karakiewicz P, Ashfaq R, Isbarn H, Fradet Y, Bastian P, Nielsen M, Capitanio U, Jeldres C, Montorsi F, Lerner S, Sagalowsky A, Cote R and Lotan Y (2018) Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder CancerJournal of Urology, VOL. 183, NO. 1, (68-75), Online publication date: 1-Jan-2010.Shariat S, Bolenz C, Godoy G, Fradet Y, Ashfaq R, Karakiewicz P, Isbarn H, Jeldres C, Rigaud J, Sagalowsky A and Lotan Y (2018) Predictive Value of Combined Immunohistochemical Markers in Patients With pT1 Urothelial Carcinoma at Radical CystectomyJournal of Urology, VOL. 182, NO. 1, (78-84), Online publication date: 1-Jul-2009. Volume 177Issue 2February 2007Page: 481-487 Advertisement Copyright & Permissions© 2007 by American Urological AssociationKeywordsimmunohistochemistrydisease progressiondeathcarcinomatransitional cellretinoblastomaMetricsAuthor Information Shahrokh F. Shariat Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. Supported by the Austrian Program for Advanced Research and Technology. More articles by this author Raheela Ashfaq Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. More articles by this author Arthur I. Sagalowsky Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Nothing to disclose. More articles by this author Yair Lotan Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with Matritech Inc. and Boehringer Ingelheim. 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