STROMAL-VASCULAR PARAMETERS FOR PROLIFERATIVE LEIOMYOMAS OF THE BODY OF UTERUS IN WOMEN WITH REPRODUCTIVE PERIOD IN THE ASPECT OF AGE

Abstract

Leiomyoma of the body of uterus is a tumor of unknown etiology, the frequency of which ranges from 5.4% to 77.0% and 80.0% of patients suffer from this problem during their lifetime. Despite the researches conducted up to date, the etiology of leiomyoma is still largely unknown and treatment strategy is limited due to the lack of information on the pathogenesis of this disease. Objectives and methods: 1. Ultrasonographic examination of leiomyoma nodes with color doppler mapping and resistance index detection. 2. Staining of preparations with hematoxylin and eosin to determine histostructure. 3. Staining of preparations with Masson Trichrome for detection of extracellular matrix. The percentage rate of fibrotic changes in the node was evaluated using the ImageJ program by processing the preparations stained with MASSON TRICHROME through a special algorithm. 4. Immunohistochemical evaluation of angiogenesis using CD34 marker. Morphometric analysis of blood vessels was performed with the special algorithm of CellProfiler program. The obtained results were processed by the computer program package of mathematical statistics - SPSS-21. Pearson x2 was used to check the confidence. Conclusions: 1. In the period before the nodes of uterine leiomyoma, a reshaped vascular collector is formed with sharp vascularization, which is a cover; and creates an ideal environment in the process of growth and development of leiomyoma; The growth of nodes up to 1 cm proceeds by diffusion from the adjacent muscle within the collector, as an independent autonomous unit, in conditions of scarcity of internal angiogenesis in the nodes (angiogenesis 45%, RI-0.48). 2. In nodes of proliferative leiomyoma with the size of up to 2 cm, there is an increase in internal (intranodal) vascularization, which confirms the active role of angiogenesis in the process of growth and development of leiomyoma; 3. Along with the growth of leiomyomas up to 3 cm, both in the muscle adjacent to the nodes (RI-0.61) and in the internal tissue of the nodes, there is a decrease in angiogenesis up to 25.6%, (RI-0.63); and in nodules up to 4 cm, a dramatic decrease in angiogenesis in the adjacent muscle (RI-0.53) and intranodal tissue up to 15.8% (RI-0.42). The mentioned fact confirms the complete exhaustion of the resources of remodeled blood vessels formed during the growth and development of leiomyoma within the collector by forming a hypoxic condition in the nodes. 4. In the proliferative, small growing leiomyomas, the proliferative activity of fibroblasts with the formation of extracellular matrix and the reproduction of fibrotic tissue is directly proportional to the age of the patient - with their decrease up to 30 years, and with increasing of age, the volume increases. 5. Immunohistochemically (with the expression of SD 34), a high rate of the number and area of ​​blood vessels detected in nodes at a young age, and a large diameter of blood vessels in patients at the age of 41-49, confirms the activation of angiogenesis at a young age with the formation of predominantly small-caliber arteries (arterioles) and capillaries, which is the basis for the active growth of nodes at a young age, in contrast to patients at the age of 41-49 with a high index of the average diameter of blood vessels; 6. The presence of small-diameter blood vessels indicates the maximum ability of the thinnest capillaries to reproduce and the possibilities to form anastomoses. Capillaries, as the thinnest tubes, represented by only one layer of endothelium, contribute to the activation of oxygen and metabolism in tissues and represent an important link in the molecular mechanisms of leiomyoma growth and development. 7. In line with the increase in the size of proliferative leiomyomas, the increase in the volume of the extracellular matrix with the decrease of angiogenesis and the development of hypoxia leads to create an obstacle for growth and development in the node with the onset of a remission period. 8. The high potential of self-renewal, differentiation, regeneration of blood vessels and constant active changes in the body of the uterus and within the node should be taken into consideration, as a hormone-dependent process in terms of the formation of new remodeled blood vessels, which is an important factor in the development of relapse. In addition, the active involvement of intranodal hypoxia and extracellular matrix in the process of remodeling blood vessels cannot be excluded.