Yurakh A. Prediction of urothelial bladder cancer clinical course by molecular and immunohistochemical analysis of cell-cycle regulators.

Thesis is devoted to the prognostication of clinical course of urothelial bladder cancer. Molecular alteration of INK4A/ARF, INK4B, p53, CCND1, CDK4, MDM2 genes and alteration p14ARF, p16INK4A, p21Waf1, p27Kip1, pRb, MDM2 and Ki-67 protein expression were studded by molecular and immunohistochemical methods accordingly. CCND1 gene amplification and higher level of proteins p16INK4A, p21Waf1, p27Kip1 and cyclin D1 expression were observed in papillary tumor in comparison with sessile. Cell proliferation was related with p53 immunoreactivity for papillary and with p21Waf1/Cip1 expression for sessile tumors. Difference in prognostic factors between papillary and sessile tumors was shown. Deletions of INK4A/ARF gene and loss of p14ARF protein expression was described as recurrence prognosticator for papillary tumors. The loss of p14ARF expression with the tumor stage is the independent prognosticator of progression, and with grade - overall survival of patients with papillary urothelial bladder cancer. Otherwise, loss of protein p27Kip1 expression is a progression prognosticator and Ki-67 protein is prognosticator of overall survival for patients with sessile tumor.