Buchynska L. Endometrial cancer: taxonomy of genetic changes of tumor cells and their role in determination of malignant potential

The present work is devoted to the solution of actual problem of modern oncology - determination of a role of genetic and molecular biological markers in formation of the malignant phenotype of endometrial adenocarcinoma, as a background for aggressiveness of malignant process and disease outcome. This work is performed on operation materials, aspirates and scraping of uterine cavity, peripheral blood lymphocytes of 267 patients with endometrial cancer (EC) stage I (T1N0M0), 71 patients with endometrial glandular hyperplasia (EGH) and 31 healthy donors (control). In the study was used the following methods: morphological, cytological, histo- and cytochemical, cytospectrophotometrical, morphometrical, immunohistochemical, indirect fluorescence, cytogenetical, clinical, genealogical and statistical. For the first time, the structural, functional, and molecular biological changes in EC cells of the same histological structure (endometrioid adenocarcinoma) were studied and systematized. The heterogeneity of cell population was shown by a set of cytogenetic markers (chromatin structure, ploidy, nucleolar organizer regions, mitotic activity) and by differential expression of biomarkers (р53, p21WAF1/CIP1, р16INK4a, MDM2, p14ARF, Кi-67). These markers adequately reflect the proliferative potential of EC and EGH, correlate both with depth of myometrial invasion the 5-year survival of patients. It was revealed that the morphofunctional changes in nucleolus could be used for assessment of hormonal pathomorphosis under the treatment of EC and EGH patients by progestines. It was shown that nucleolar organizer regions of chromosomes and a frequency of chromosome associations are increased in the peripheral blood lymphocytes of EC patients, that reflects genome destabilization in somatic nonmalignant cells. It was defined the complex of cytomorphological and molecular-biological criterias of EC malignancy that are relevant for the assessment of indivіdual prognosis of tumor processes.