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RESEARCH PRODUCT

Immunohistochemical expression of Ki-67, Cyclin D1, p16INK4a, and Survivin as a predictive tool for recurrence and progression-free survival in papillary urothelial bladder cancer pTa / pT1 G2 (WHO 1973)

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Objectives: To investigate the expression of several immunohistochemical (IHC) markers and their predictive ability for the recurrence-free and progression-free survival of papillary urothelial bladder cancer (UBC) pTa/pT1 G2 (WHO 1973) compared to classical anatomo-clinical variables using a multidimensional analysis. Materials and Methods: A population-based cohort of 213 primary stage UBC (pTa/pT1) G2 (WHO 1973) was evaluated by classic anatomopathological variables and characterized by immunohistochemistry (23 IHC markers, representative of different oncogenic pathways). The most important variables as a predictor of recurrence-free and progression-free survival were selected using multidimensional statistical models, such as random survival forests and least absolute shrinkage and selection operator (. Recurrence and progression-free survival of the previously selected variables were also calculated. Results: Mean follow-up was 58 +/- 33.5 months. Recurrence and progression rates were 54.5% (n = 116) and 17,4% (n = 37), respectively. The most influential variables in the low recurrence-free survival were in order: number of resected tumors, high expression of Ki67 (> 10%), Cyclin D1 (> 10%), and low cytoplasmic staining of p16INK4a. Regarding low progression-free survival, the most important variables were Ki67 (> 15%), multicentric tumor arrangement and Survivin nuclear expression (> 20%). Kaplan-Meier and cox-regression model analyses showed that the variables selected by multidimensional models were able to discriminate the clinical outcome. Conclusions: Ki67 index is the most useful IHC marker, since it can improve the prediction of both recurrence and progression-free survival in papillary UBC pTa/pT1 G2 (WHO 1973). There are other markers, whose utility is specific to recurrence-free survival, such as Cyclin D1 and p16INK4a or in progression-free survival, such as Survivin. (C) 2018 Elsevier Inc. All rights reserved.