title: p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder.
abstract: OBJECTIVE
  Although the majority of patients with node positive transitional cell carcinoma of the bladder have disease progression, a definitive subset is cured by surgery only. Nuclear accumulation of p53 has been associated with disease progression in patients with superficial transitional cell carcinoma and decreased survival in those with muscle invasive disease. We determined whether p53 status would predict survival in a cohort with nodal metastasis.
  
  
  METHODS
  We explored the comprehensive database of all 199 radical cystectomies performed at our institution between July 1988 and September 1999. The 59 patients in this database with node positive pathology comprise our study. We performed immunohistochemical analysis of specimens using the MAB1801 antibody with greater than 20% lymph node and primary tumor nucleus staining deemed positive. Additional covariates measured included patient age, sex, pathological disease stage, adjuvant chemotherapy and nodal stage. Disease-free survival curves were generated for the various covariates and compared using the log rank test. The Cox proportional hazards technique was used to determine covariate adjusted p53 survival.
  
  
  RESULTS
  In the cohort overall median disease-free survival was only 21 months, although 18% of patients were disease-free at 5 years. There was evidence of p53 nuclear accumulation in 54% of cases and complete agreement of nodal with bladder p53 nuclear accumulation. No significant baseline differences were noted in the covariates with respect to p53 nuclear accumulation. For stratum specific disease-free survival univariate and multivariate analyses revealed that only pathological stages p0-p2b versus p3-p4 (hazards ratio 2.86, p = 0.03), and nodal stages N2 versus N1 and N3 versus N1 (hazards ratio 3.84, p = 0.01 and hazards ratio 13.3, p = 0.0002, respectively) were significantly associated with prolonged disease-free survival, while p53 nuclear accumulation was not.
  
  
  CONCLUSIONS
  Despite credible evidence for p53 nuclear accumulation prognostication in patients with in situ and invasive transitional cell carcinoma, this marker is not predictive of disease-free survival in node positive disease.
authors.affiliation: Departments of Surgery (Urology) and Anatomic Pathology, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Fleshner
authors.forename: L
authors.initials: L
authors.lastname: Kapusta
authors.forename: D
authors.initials: D
authors.lastname: Ezer
authors.forename: S
authors.initials: S
authors.lastname: Herschorn
authors.forename: L
authors.initials: L
authors.lastname: Klotz
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D016159:Tumor Suppressor Protein p53