Andriiv A. Prognostic and predictive value of Na+/I- symporter in breast cancer patients

Thesis is devoted to the actual problem of oncology - the study of the features of the expression of Na+/I- symporter in tumor cells in the in vitro system and ex vivoon clinical material, and substantiation of its significance for estimating the cancer course prognosis, the sensitivity to anthracycline-containing therapy in breast cancer (BC) patients with various molecular subtypes. In the in vitro experimental system, the highest expression rates of iodine symporter were detected in the cell cytoplasm MDA-MB-231, MDA-MB-468 and MCF-7 / Dox cells (248 ± 1.9, 272 ± 3.2, and 289 ± 2,8 points, respectively) of the basal molecular subtype. In the luminal A and B BC cells lines T47D and MCF-7, low expression of NIS (73 ± 2.0 and 115 ± 1.9 H-score points, respectively) were established predominantly on the plasma membrane of cells. In the clinical specimen, it was found that NIS expression in tumor cells from BC patients with luminal B and basal subtypes correlated with the stage of the disease (r = 0.46 and 0.46, respectively), presence of metastases in regional lymph nodes (r = 0.49 and 0.53, respectively) and degree of tumors differentiation (r = -0 , 57 and -0.62 respectively, p <0.05). It was found that BC patients with luminal B and basal subtypes in the presence of NIS, N-cadherin, CD44, and lack of expression of E-cadherin with the high proliferative activity of tumor cell were characterized by lower 5-year relapse-free survival. It was proved that 3-year relapse-free survival of BC patients with luminal B and basal subtypes is higher in the absence of NIS expression in tumors. The possibility of using NIS expression indicators in tumor cells was grounded for predicting the aggressiveness of the BC course of various molecular subtypes and as a predictive marker of neoadjuvant polychemotherapy efficiency.