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: Multitissue-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 substage 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. Conclusion: 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. (c) 2004 Elsevier B.V. All rights reserved.