title: Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement.
abstract: BACKGROUND
  The effect of p53 protein expression and MIB-1 proliferative activity on survival and chemotherapeutic response in patients with lymph node (LN)-positive transitional cell carcinoma (TCC) of the urinary bladder remains unclear. The objective of this study was to assess the ability of these markers to predict disease-associated outcomes and response to chemotherapy in a cohort of patients with LN-positive TCC.
  
  
  METHODS
  The authors examined the expression of p53 and MIB-1 in the LN metastases from 139 patients who underwent cystectomy for TCC at their institution. P53 and MIB-1 nuclear staining were quantified using an image-analysis system. Cox proportional hazards regression models were used to test associations of these markers with death from TCC, distant metastases, and local recurrence for all patients and in the subset of patients who were treated with adjuvant chemotherapy.
  
  
  RESULTS
  The median p53 and MIB-1 indices were 45.2% and 30.3%, respectively. The median follow-up was 4.5 years (range, 0.1-10 years). There were no statistically significant associations noted between the p53 and MIB-1 indices and the outcomes studied. When the analysis was limited to patients who were treated with adjuvant chemotherapy (n = 37 patients), the p53 index was found to have no prognostic value; however, there was a significant association between MIB-1 and distant metastases (P = 0.049). When disease-specific survival rates were stratified according to p53 index and chemotherapy, patients exhibited a response to chemotherapy regardless of p53 index.
  
  
  CONCLUSIONS
  p53 and MIB-1 were not found to be associated significantly with disease-related outcomes in patients with LN-positive TCC. Adjuvant chemotherapy appeared to be effective regardless of p53 status. MIB-1 may prove useful in predicting response to chemotherapy.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA. frank.igor@mayo.edu
authors.forename: Igor
authors.initials: I
authors.lastname: Frank
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sebo
authors.forename: Ajay
authors.initials: A
authors.lastname: Nehra
authors.forename: Horst
authors.initials: H
authors.lastname: Zincke
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015653:Cystectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53