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)

• Published in: Urologic oncology 2019-02, Vol.37 (2), p.158-165
• Main Authors: March-Villalba, José Antonio, Ramos-Soler, David, Soriano-Sarrió, Pilar, Hervás-Marín, David, Martínez-García, Laura, Martínez-Jabaloyas, José María
• Format: Article
• Language: English
• Subjects: Bladder cancer; Clinical outcome; Immunohistochemistry; Multidimensional analysis; Stage Ta/T1
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2018.10.005

•It is possible to classify Papillary Urothelial bladder cancer pTa/pT1 G2 (WHO 1973) in risk groups according to immunohistochemical markers.•Ki-67 index is the most useful IHC marker since it can improve the prediction of both recurrence and progression-free survival in papillary Urothelial bladder cancer 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.•These IHC markers, especially Ki-67, could be used in daily clinical Urothelial bladder cancer pTa/pT1 G2 (WHO 1973) management. 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. 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. 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. 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. [Display omitted]