title: Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder.
abstract: OBJECTIVE
  To determine whether p53 and p21 expression in bladder carcinoma in situ (CIS) with or without papillary disease can predict disease recurrence, progression, and survival.
  
  
  METHODS
  Immunohistochemical staining for p53 and p21 was carried out on paraffin-embedded tumor specimens from 47 and 39 patients, respectively, who had CIS with or without Ta or T1 disease, but without muscle-invasive cancer. Immunoreactivity was categorized as either positive (reactivity in 10% or more CIS cells) or negative.
  
  
  RESULTS
  Expression of p53 and p21 was positive in 28 (60%) of 47 and 12 (31%) of 39 CIS tumors, respectively. p53 expression was not associated with clinical outcome. Positive p21 expression was associated with bladder cancer recurrence (P = 0.035) and progression (P = 0.033) when adjusted for the effects of clinical stage and grade. The combined p53/p21 expression status was independently associated with disease recurrence (P = 0.022), progression (P = 0.042), and cancer-specific survival (P = 0.031). Patients with p53+/p21+ expression were at significantly greater risk of disease recurrence, progression, and mortality than those having a p53+/p21- or p53-/p21- phenotype (not significantly different from each other statistically).
  
  
  CONCLUSIONS
  In CIS without muscle-invasive disease, positive p21 expression was independently associated with bladder cancer recurrence and progression. Positive expression for both p53 and p21 puts patients with bladder CIS at the greatest risk of bladder cancer recurrence, progression, and, most importantly, mortality, suggesting a potential rationale for early definitive therapy in these patients. On the other hand, an intact pathway at the level of p21 seems to abrogate the detrimental effects of altered p53 immunoreactivity on the outcome of bladder CIS.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine and Methodist Hospital, Houston, Texas, USA.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: JaHong
authors.initials: J
authors.lastname: Kim
authors.forename: Grigorios
authors.initials: G
authors.lastname: Raptidis
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000235:genetics / Q000401:mortality; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012727:Sex Characteristics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53