title: Combined p21WAF1/CIP1 and p53 overexpression predict improved survival in muscle-invasive bladder cancer treated by radical radiotherapy.
abstract: OBJECTIVE
  The prognostic value of p21 and p53 expression was evaluated for patients with muscle-invasive bladder cancer treated by radical radiotherapy.
  
  
  METHODS
  Sixty-eight paraffin-embedded sections from surgically resected tumors taken prior to irradiation were immunostained for p21 and p53.
  
  
  RESULTS
  Nuclear staining for p21 and p53 was demonstrated in 32/68 (47%) and 46/68 (68%) tumors, respectively. There was no correlation between p21 and p53 immunopositivity in this group (r = 0.067, p = 0.56). Patients were stratified into four distinct groups depending on staining for p21 and p53: p21+p53+, p21+p53-, p21-p53+, and p21-p53-. Patients with p21+p53+ tumors had the best prognosis with a 3-year survival of 82% compared to 12% for p21-p53+ tumors (p = 0.0031), 29% for p21+p53- tumors (p = 0.0108); and 45% for p21-p53- tumors (p = 0.0375). The p21+p53+ group also demonstrated significantly improved survival when a combined analysis was performed of p21-p53+, p21-p53-, and p21+p53- tumors (3-year survival = 30%, p = 0.0062). In a multivariate model, p21+p53+ tumors (p = 0.0108, relative risk [RR] = 5.18) and complete/partial response (p = 0.0019, RR = 3.76) were the only independent predictors of improved survival.
  
  
  CONCLUSIONS
  With muscle-invasive bladder tumors treated by radical radiotherapy, stratification for p21 and p53 identifies distinct prognostic groups, with p21+p53+ tumors being associated with the best survival and p21-p53+ the worst.
authors.affiliation: Department of Surgery, The Medical School, University of Newcastle, Newcastle-upon-Tyne, United Kingdom. khaverqureshi@hotmail.com
authors.forename: K N
authors.initials: KN
authors.lastname: Qureshi
authors.forename: T R
authors.initials: TR
authors.lastname: Griffiths
authors.forename: M C
authors.initials: MC
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Marsh
authors.forename: J T
authors.initials: JT
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Lunec
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
authors.forename: J K
authors.initials: JK
authors.lastname: Mellon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53