A comprehensive study of clinical, morphological, immunohistochemical (IHC) features of non-invasive urothelial bladder cancer (NIUBC) and their relationships with the processes of epithelial-mesenchymal transformation (EMT) of tumor cells to improve the criteria for predicting the course of the disease was carried out.
Based on a comprehensive pathomorphological study, the main clinical-morphological, histological and IHC indicators of the prognosis of NIUBC are determined. The immunological features in NIUBC, EMT processes in tumor cells were studied and the relationship between these processes was established, and their significance in the recurrence and progression of the disease was determined. For the first time, a new classification of the stages of EMT in NIUBC has been proposed, which is based on a comparative analysis of the expression levels of epithelial (CС-20, CС-7, E-cadherin) and mesenchymal (vimentin, N-cadherin) markers by cells of the tumor epithelial layer. The relationship between the stages of EMT and the prognosis of the disease was revealed: for cancers with recurrence without progression, the first stage of EMT of tumor cells is characteristic, and for cancers with relapse and progression of the disease, the second stage of EMT.
Supplemented data on the role of the immune system in the progression of the disease. It was established that NIUBC with recurrence and progression was characterized by severe infiltration of CD3+ and CD8+ T-lymphocytes compared with non-recurring ones. The involvement of immunocompetent cells in EMT processes was revealed, which consists in an increase in the degree of infiltration of CD68+ by macrophages, CD + T-lymphocytes, including both CD8+ and CD4+ cells when EMT appears in the tumor.
The predictive value of the EORTC system has been confirmed. It was established that unfavorable risk criteria for recurrence of NIUBC are: tumor size more than 3 cm, multifocal growth, total score 5–9 according to the EORTC algorithm, the first stage of EMT. The criteria for recurrence with progression of NIUBC should be considered: tumor size greater than 3 cm, multifocal growth, total score 14–23 according to the EORTC algorithm, Ki-67 mark index 21–50%, moderate p53 expression, increased infiltration of CD3+ and CD8+ lymphocytes, the second stage of EMT.
The panel of IHC markers was optimized and recommended for determining the aggressive potential of NURMP: p53, Ki-67, MMP-9, CD3+, CD8+, CD68+.
