title: P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma.
abstract: OBJECTIVE
  To evaluate the prognostic impact of p16 immunoreactivity in minimally invasive transitional cell bladder carcinomas (stage T1).
  
  
  METHODS
  Multi-tissue-arrays containing 73 samples of T1 bladder carcinomas were stained immunohistochemically for p16. Additionally, p53 and Ki-67 antigen expression were examined. A multivariate analysis including other prognostically relevant factors like tumor grade and sub-stage was performed.
  
  
  RESULTS
  Loss of p16 expression occurred in 54% of cases and was significantly associated with reduced progression-free (p=0.018 by univariate analysis), but not with recurrence-free survival (p=0.341). Median Ki-67 antigen and p53 index were 51% (range, 1-93%) and 10% (range, 0-100%), respectively. Both indices correlated significantly (p=0.041 and p=0.024, respectively) with recurrence-free, but not with progression-free survival. Also tumor grade was significantly associated with tumor recurrence (p=0.006). By multivariate analysis, tumor grade (p=0.008) was identified as an independent predictor of tumor recurrence, whereas p16 expression (p=0.009) was identified as an independent predictor of tumor progression.
  
  
  CONCLUSIONS
  According to our data, there is a significant correlation between loss of p16 expression and tumor progression in patients with minimally-invasive bladder cancer. Immunohistochemical p16 staining may therefore represent a useful tool of providing additional information on the clinical outcome of these patients.
authors.affiliation: Institute of Pathology, University of Schleswig-Holstein (Campus Lübeck), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Anne
authors.initials: A
authors.lastname: Mahnken
authors.forename: Ingo
authors.initials: I
authors.lastname: Kausch
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology*; D008297:Male; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53