The Georgian Biomedical News Downloaded from gbmn.org. For personal use only. No other uses without permission. Copyright © 2022. All rights reserved. VOLUME 1. ISSUE 1. JANUARY-MARCH 2023 2023 Peculiarities of Angiogenesis of the Uterine Body Leiomyomas in Women of Reproductive Age Mindia Iobashvili 1 , Marina Pailodze 2 , Irma Jikia 3 , Anzor Gogiberidze 2 , Nikoloz Vachadze 2 , Magda Tortladze 4 , Evgeni Asatiani 2 BACKGROUND Despite recent achievements regarding the pathogenesis of leiomyoma, the exact mechanisms and role of angiogenesis are not well understood. According to the existing evidence, the excess of steroids, their influence on the apoptosis mechanisms, and the expression of local growth factors may stimulate the formation of leiomyomas in women of reproductive age. OBJECTIVES The present study aimed to ascertain the pathophysiological mechanisms underlying angiogenesis disorders and shed light on the function of steroids in this process. METHODS The central and peripheral parts of the 42 postsurgical uterine leiomyoma nodes were examined with the aim of assessment of angiogenetic changes in the proliferating, recurrent, and latent leiomyomas, using (i) hematoxylin and eosin (H and E), and Masson’s trichrome stain of formalin-fixed paraffin-embedded sections, and (ii) immunohistochemistry evaluation of estrogen receptor (ER), progesterone receptor (PR), and CD34 (transmembrane phosphoglycoprotein protein encoded by the CD34) markers. RESULTS The small proliferative leiomyomas (1-2 cm) are characterized by prominent angiogenesis with a dominance of small and medium-caliber aberrant vessels. The tendency to decrease intranodal blood vessels with the growth of tumor nodes (3-4 cm in size) indicates to depletion of resources of the autonomous vascular collector (tumor bed), after which the leiomyomata may enter the recurrence phase with the formation of a new locus of angiogenesis. The uniform distribution of the blood vessels throughout the proliferative leiomyoma node indicates that tumor growth occurs throughout the whole vascular collector. The depletion of the capacity of angiogenesis has an inhibitory effect on the growth of latent nodes and increases the risk of the secondary lesion because of blood supply alterations. CONCLUSIONS Angiogenesis plays an important role in the progression of leiomyoma. The tumor growth occurs throughout the whole vascular bed (in the central and peripheral parts of the leiomyomata) and not from a single smooth muscle cell. KEYWORDS CD34 marker; estrogen receptor (ER); latent leiomyoma; progesterone receptor (PR); proliferating leiomyoma; recurrent leiomyoma; uterine body leiomyoma. BACKGROUND ccording to the existing evidence, angiogenesis is an essential element in the regulation of tumor growth. 1 It is well known that leiomyomas are characterized by markedly remodeled, diminished number of vessels compared to the surrounding healthy myometrium, 2 which causes severe hypoxia of the tumorous tissue. 3 There is evidence of a decrease in the function of angiogenic growth factors in the case of leiomyoma as well. There are various viewpoints regarding the growth of leiomyomas in the uterine body. 4-8 The myometrium experiences active myocyte proliferation and myometrial hyperplasia (MMH). The majority of leiomyomas develop in hypoxic sites of MMH, which is recognized as a precursor of leiomyoma. 9,10 The small leiomyomas are less vascular compared to myometrium, 11,12 and the smallest (1-3 mm) ones are almost avascular with nodular growth due to diffusion from the surrounding myometrial vascular network. 13 According to existing considerations the excess of steroids, alterations of the apoptosis mechanisms, and expression of local growth factors may increase the frequency of leiomyomas in women of reproductive age. 14-17 Despite recent achievements in the knowledge of the pathology exact mechanisms of leiomyoma is still obscure, the precise role of leiomyoma precursor cells is not well understood, and the radical hysterectomy is the only successful treatment option because of the ineffectiveness of conservative measures. In the present study, we aimed to ascertain the pathophysiological mechanisms underlying angiogenesis disorders and shed light on the function of steroids in this process. ABSTRACT A