title: p53 expression in patients with advanced urothelial cancer of the urinary bladder.
abstract: OBJECTIVE
  To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease-specific survival in a multi-institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB).
  
  
  METHODS
  The study comprised 692 patients with pT3-4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap-corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy.
  
  
  RESULTS
  p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer-specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer-specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer-specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model.
  
  
  CONCLUSIONS
  While assessing p53 expression has limited utility in patients with lymph node-positive UCB, it marginally improves prognostication in patients with advanced non-metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.
authors: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. sfshariat@gmail.com
authors: Shahrokh F
authors: SF
authors: Shariat
authors: Christian
authors: C
authors: Bolenz
authors: Pierre I
authors: PI
authors: Karakiewicz
authors: Yves
authors: Y
authors: Fradet
authors: Raheela
authors: R
authors: Ashfaq
authors: Patrick J
authors: PJ
authors: Bastian
authors: Matthew E
authors: ME
authors: Nielsen
authors: Umberto
authors: U
authors: Capitanio
authors: Claudio
authors: C
authors: Jeldres
authors: Jérôme
authors: J
authors: Rigaud
authors: Stefan C
authors: SC
authors: Müller
authors: Seth P
authors: SP
authors: Lerner
authors: Francesco
authors: F
authors: Montorsi
authors: Arthur I
authors: AI
authors: Sagalowsky
authors: Richard J
authors: RJ
authors: Cote
authors: Yair
authors: Y
authors: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000473:pathology
chemical_list: D016159:Tumor Suppressor Protein p53