EXPRESSION OF SIGNALING MOLECULES (P53, COLLAGEN TYPE II, VEGF AND VEGFR) IN BIOPTS OF INTACT MYOMETRY IN WOMEN OF DIFFERENT AGES

DOI: https://doi.org/10.29296/25877305-2021-09-16
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Issue: 
9
Year: 
2021

A. Shapovalova(1); Professor V. Polyakova(2, 3), Doctor of Biological Sciences, Professor of
the Russian Academy of Sciences; T. Kleimenova(2), Candidate of Biological Sciences (1)Saint Petersburg
Institute of Bioregulation and Gerontology (2)Saint Petersburg State Pediatric Medical University, Ministry
of Health of Russia (3)Belgorod National Research University

The aim of the study. To study the correlation of expression of p53, type II collagen, VEGF and VEGFR in biopsy specimens of intact myometrium in women of different age groups. Materials and methods. The study included 90 patients aged 23 to 47 years, who were randomized into 6 groups. The first three groups included 45 practically healthy patients, the fourth, fifth and sixth groups – women with diagnosed uterine myoma, as a result of which the presence of two diametrically opposite variants of the development of myoma nodes in reproductive age was confirmed – simple myoma and proliferating myoma, with the latter variant predominating. Immunofluorescence and morphometric analysis of p53 proteins, type II collagen, VEGF and VEGFR using Olympus FV1000. Results. The average relative area of the p53 expression level was lower in all three age groups compared to the control group. The VEGF level turned out to be statistically significantly higher in proliferating fibroids in women, which indicated an intensification of the neoangiogenesis process in active uterine fibroids in younger women. The level of type II collagen was higher in all age groups in patients with uterine fibroids. Conclusion. The revealed features of proliferation, apoptosis and neoangiogenesis indicate new aspects of pathogenetically substantiated therapy for uterine fibroids. It becomes possible to develop drugs that contribute to the inhibition of the processes of proliferation, neoangiogenesis and stimulation of apoptosis. Apparently, this group of drugs will occupy an important place in therapeutic agents for conservative treatment at the initial stage of the development of myomatous nodes in young women.
Keywords: 
oncology
gynecology
leiomyomas
apoptosis
proliferation
angiogenesis
growth factors

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References: 
  1. Reis F.M., Bloise E., Ortiga-Carvalho T.M. Hormones and pathogenesis of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2016; 34: 13–24. DOI: 10.1016/j.bpobgyn.2015.11.015
  2. Sparic R., Mirkovic L., Malvasi A. et al. Epidemiology of Uterine Myomas: A Review. Int J Fertil Steril. 2016; 9 (4): 424–35. DOI: 10.22074/ijfs.2015.4599
  3. Wise L.A., Palmer J.R., Stewart E.A. et al. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women’s Health Study. Obstet Gynecol. 2005; 105 (3): 563–8. DOI: 10.1097/01.AOG.0000154161.03418.e3
  4. Taran F.A., Wallwiener M., Kabashi D. et al. Clinical characteristics indicating adenomyosis at the time of hysterectomy: a retrospective study in 291 patients. Arch Gynecol Obstet. 2012; 285 (6): 1571–6. DOI: 10.1007/s00404-011-2180-7
  5. Fernandez H., Capmas P., Lucot J.P. et al.; GROG. Fertility after ectopic pregnancy: the DEMETER randomized trial. Hum Reprod. 2013; 28 (5): 1247–53. DOI: 10.1093/humrep/det037
  6. Fleischer R., Weston G.C., Vollenhoven B.J. et al. Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation. Best Pract Res Clin Obstet Gynaecol. 2008; 22 (4): 603–14. DOI: 10.1016/j.bpobgyn.2008.01.005
  7. Strizhakova M.A., Panov V.O., Uvarova E.V. i dr. Magnitno-rezonansnaja tomografija: vozmozhnosti issledovanija organov mochepolovoj sistemy u devochek s porokami razvitija i ob'emnymi obrazovanijami vnutrennih genitalij. Reproduktivnoe zdorov'e detej i podrostkov. 2005; 1: 44–52 [Strizhakova M.A., Panov V.O., Uvarova E.V. et al. Magnetic resonance imaging: the possibilities of studying the organs of the genitourinary system in girls with malformations and volumetric formations of the internal genitals. Reproductive health of children and adolescents. 2005; 1: 44–52 (in Russ.)].
  8. Downes E., Sikirica V., Gilabert-Estelles J. et al. The burden of uterine fibroids in five European countries. Eur J Obstet Gynecol Reprod Biol. 2010; 152 (1): 96–102. DOI: 10.1016/j.ejogrb.2010.05.012
  9. Stănescu A.D., Nistor E., Sajin M. et al. Immunohistochemical analysis in the diagnosis of uterine myometrial smooth muscle tumors. Rom J Morphol Embryol. 2014; 55 (3 Suppl): 1129–36.
  10. Hewedi I.H., Radwan N.A., Shash L.S. Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors. Diagn Pathol. 2012; 7: 1. DOI: 10.1186/1746-1596-7-1
  11. Czarkowska-Paczek B., Przybylski J. Mechanizmy gojenia uszkodzonych tkanek [Mechanisms of tissue repair]. Przegl Lek. 2004; 61 (1): 39–42.
  12. Iwahashi M., Muragaki Y. Increased type I and V collagen expression in uterine leiomyomas during the menstrual cycle. Fertil Steril. 2011; 95 (6): 2137–9. DOI: 10.1016/j.fertnstert.2010.12.028
  13. Zbucka M., Miltyk W., Bielawski T. et al. Mechanism of collagen biosynthesis up-regulation in cultured leiomyoma cells. Folia Histochem Cytobiol. 2007; 45 (Suppl 1): S181–5.
  14. Berto A.G., Sampaio L.O., Franco C.R. et al. A comparative analysis of structure and spatial distribution of decorin in human leiomyoma and normal myometrium. Biochim Biophys Acta. 2003; 1619 (1): 98–112. DOI: 10.1016/s0304-4165(02)00446-4
  15. Chung Y.J., Chae B., Kwak S.H. et al. Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro. Int J Med Sci. 2014; 11 (3): 276–81. DOI: 10.7150/ijms.7627
  16. Plewka D., Morek M., Bogunia E. et al. Expression of VEGF isoforms and their receptors in uterine myomas. Ginekol Pol. 2016; 87 (3): 166–77. DOI: 10.17772/gp/60979