P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma.
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.
Krüger
Stefan
S
Institute of Pathology, University of Schleswig-Holstein (Campus Lübeck), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Mahnken
Anne
A
Kausch
Ingo
I
Feller
Alfred C
AC
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*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53