Iurchenko N. Molecular-biological features of endometrial cancer in patients with aggregation of tumor pathology in pedigrees

In the dissertation, the obtained results are described, which show that the biological heterogeneity of endometrial cancer (EC) at the stage I and II is related to the genealogical anamnesis of EC patients. This, and also a molecular tumor phenotype and factors of tumor microenvironment can determine the degree of tumor malignancy and the course of disease. We have found that in 20.5% of pedigree of EC patients there is accumulation of malignant neoplasms of different genesis, with a prevalence of cancer of the female reproductive organs and the gastrointestinal tract (73.3%). We also could characterize the morphological and immunohistochemical features of EC patients with a family history of cancer. We have shown that the majority of EC patients with and without aggregation of oncological pathology in pedigrees the moderately differentiated tumors are diagnosed (in 46.3% and 38.9 of cases, respectively). Also, such tumors show the deep invasion in myometrium (58.5% and 64.8 %, respectively). Moreover, in EC patients with the family history of cancer a significant increase in a proportion of cells, expressing the tumor suppressor protein FOXP3 and p16INK4a, the smaller number of cells expressed p53, Ki-67 (a marker for proliferating cells) and tumorinfiltrating FOXP3+ -lymphocytes, in comparison with patients without tumor aggregation in pedigrees. For the first time, we have found that the 5-year survival rate of EC patients with the family history of cancer is higher, compared to that in EC patients without aggregation of oncological pathology in the pedigree (92.0% vs. 73.0%, p<0.05). We have shown that the most informative prognostic markers of the course of disease of EC patients with the family history of cancer are: the number of tumor-infiltrating FOXP3+- lymphocytes and the Ki-67 expression.