Dubinina V. Prognosis and early diagnosis of tumorous diseases of the endometrium.

The presented work deals with increase of efficacy of individual prevention and prognosis of development of tumorous diseases of the endometrium in women with hereditary determination and patients with verified pathology of the endometrium and formation of the theoretical base for introduction of molecular-genetic methods as a foundation of the model of the general system of early diagnosis and prevention of oncological diseases. It is established that the most influential risk factors of development and progressing of tumorous pathology of the endometrium are considered to be metabolism disturbance, complicated genealogical history, trauma of the uterine mucous membrane in the past history as well as dysfunction of the system "pituitary-ovaries-thyroid-uterine". There is high or moderate activity of NO-syntase in the endometrium of practically healthy women while activity of this enzyme is weak and tracy in most cases in hyperplastic processes of the endometrium; it is tracy or practically absent in atypical hyperplasia of the endometrium and cancer of the uterine body. Expression of estradiol receptors in the mucous membrane of the uterine body in the patients of reproductive age is reliably reducing (p<0.05) in progressing of the tumorous process from the norm to atypical hyperplasia of the endometrium. Expression of progesterone receptors in the endometrium tissue of the patients of reproductive age is reliably reducing (p<0.05) during progressing of the tumorous process from the norm to atypical hyperplasia of the endometrium. Changes in the system of cellular immunity in different tumorous transformation of the endometrium do not give characteristic distinctions and go not reflect severity of the disease but correlations of fractions of immunocompetent cells are significant for evaluation of the disease prognosis. The proposed index of tumour-specific reactivity (ITSR) is a quotient of division the percentage content of natural killers (NK) and T-cells (in the numerator) and percentage contents of Tx(in the denominator). The comparative analysis of the immune response in patients with tumorous diseases of the endometrium showed that ITSR average meaning in a group of patients with tumors statistically reliably (p=0.0053) exceeded ITSR for a group of the examined patients who did not have a diagnosed tumor. A group of patients with oncological pathology have average relative contents of cells with the phenotype CD3+CD8+ (T-suppressors/cytotoxic cells) and general percentage of lymphocytes exceeding the same indices for patients with non-oncologic profile and patients of the control group. The presence of endometrium tumor correlated with increased amount of NK-cells in blood and reduction of relative content of T-helpers compared with control. In group of patients with the complicated family oncologic anamnesis the uterine cancer incidence rate is reliably (15.8 %) higher than the tumorous pathology of another localization incidence rate. The level of spontaneous chromosome aberrations in patients with the glandular hyperplasia is reliably lower (7.1 %) than in patients with atypical hyperplasia (29.9 %) and adenocarcinoma of the endometrium (26.5 %). On the ground of the carried out research of metaphase plates of peripheral blood lymphocytes of patients with different types of tumorous transformation 30 sites of chromosome fragility were revealed. There were found four sites of fragility 1q2.5-4.1; 2q2.4-31; 4q1.5; 5q1.4 in the chromosome apparatus of patients with atypical hyperplasia and adenocarcinoma of the endometrium both with complicated family oncologic history and without it while one site 17q2.2 was only in patients with complicated family oncologic history that was evidence of genetic determination and polygenic nature of tumorous pathology of the endometrium. The molecular-genetic studies give evidence of changes in the groups of oncogenes, genes-suppressors, genes of steroid receptors and steroid genesis and genes of the detoxication system. The comparative analysis of sanogenetic profile of patients with atypical hyperplasia and adenocarcinoma of the endometrium did not reveal reliable discrepancies between the groups. The sanogenetic profile of practically healthy women was reliably (p<0.05) higher than that in other studied groups. There were revealed disturbances at the genetic chromosome, tissue and systemic levels that gave a possibility to consider tumorous diseases of the endometrium as disregulation pathology, and proposed preclinical diagnostic criteria of their development (fragile sites, microsatellite instability, index of tumour reactivity, activity of NO-syntase, state of the receptor apparatus of the endometrium). They deepen conceptions of cancerogenesis mechanism and may be applied in specialized clinical institutions. The only possibility of individual prognosis of occurance and development variant of the tumorous process of the endometrium is application of DNA-biochip that combines all possible genes that effect the occurance and development of tumorous of the endometrium.