AGE FEATURES OF THE EXPRESSION OF SIGNAL MOLECULES – PROTEIN P53, COLLAGEN TYPE II, VEGF AND VEGFR IN BIOPTATES OF INTACT MYOMETRY IN UTERINE MYOMA

DOI: https://doi.org/10.29296/24999490-2019-06-11

A.I. Shapovalova(1), A.A. Tsypurdeeva(1), M.I. Kakhiani(1), E.N. Popov(1), V.O. Polyakova(1, 2) 1-D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Mendeleevskaya line, 3, Saint-Petersburg, 199034, Russian Federation; 2-Saint-Petersburg State University, Universitetskayay Emb., 7/9, Saint-Petersburg, 199034, Russian Federation E-mail: [email protected]

Introduction. Leiomyomas also called fibroids, is the most common benign gynecological tumor in premenopausal women. The complex pathogenesis shows multiple biogenetical and multifactorial aspects to influence the etiology and growth of leiomyomas. A clinical and morpho-immunohistochemical study of 40 patients aged from 25 to 43 years with diagnosed uterine myoma was conducted. As a result, the presence of two variants of the development of myomatous nodes as simple fibroids and proliferating fibroids in the reproductive age was confirmed with the latter to be more prevailed. The myomatous node arising from progenitor muscle cells of the vascular wall is characterized by increased expression of p53 protein in women over 36 years, high expression of growth factors (VEGF and VEGFR), the formation of a capillary network and low apoptosis, which causes their rapid growth (proliferating development). 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. Methods. Immunofluorescence and morphometric analysis of p53 proteins, type II collagen, VEGF and VEGFR using Olympus FV1000. Results. The average area of p53 protein expression in the second group was higher (p>0,05) and amounted to 6,3±2,74, while in the first group it accounted of 5,0±2,14. VEGF and VEGFR levels were statistically significantly (p
Keywords: 
leiomyomas, apoptosis, proliferation, angiogenesis, growth factors

Список литературы: 
  1. Reis M., Bloise M., Ortiga-Carvalho T.M. Hormones and pathogenesis of uterine fibroid. Best Pract. Res. Clin. Obstet. Gynaecol. 2015; 34 (13–24): 25 https://doi.org/10.1016/j.bpobgyn.2015.11.015.
  2. Sparic R., Mirkovic L., Malvasi A., Tinelli A. Epidemiology of uterine myomas: a review. Int. J. Fertil. Steril. 2016; 9: 424–35.
  3. Wise L.A., Palmer J.R., Stewart E.A., Rosenberg L. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women’s Health Study. Obstet. Gynecol. 2005; 105: 563–8.
  4. Patricia G. Moorman, Phyllis Leppert, Evan R. Myers, Frances Wang, Comparison of Characteristics of Fibroids in African American and White Women Undergoing Pre-Menopausal Hysterectomy. Fertil. Steril. 2013; 99 (3): 768–76. https://doi.org/10.1016/j.fertnstert.2012.10.039
  5. Bouyer J., Job-Spira N., Pouly J., Coste J., Germain E., Fernandez H. Fertility following radical, conservative-surgical or medical treatment for tubal pregnancy: a population-based study. BJOG. 2000; 107: 714–21.
  6. Fleischer R., Weston G.C., Vollenhoven B.J., Rogers P.A. Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation. BestPract. Res. Clin. Obstet. Gynaecol. 2008; 22 (4): 603–14. https://doi.org/10.1016/j.bpobgyn.2008.01.005.
  7. Strizhakova M.A., Panov V.O., Uvarova E.V. 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. Magnitno-rezonansnaya tomografiya: vozmozhnosti issledovaniya organov mochepolovoy sistemyi u devochek s porokami razvitiya i ob’emnyimi obrazovaniyami vnutrennih genitaliy. Reproduktivnoe zdorove detey i podrostkov. 2005; 1: 44–52 (in Russian)]
  8. Downes E., Sikirica V., Gilabert-Estelles J., Bolge S.C., Dodd S.L., Maroulis C. et a.l The burden of uterine fibroids in five European countries. Eur J. Obstet. Gynecol. Reprod. Biol.. 2010; 152: 96–102. https://doi.org/10.1016/j.ejogrb.2010.05.012.
  9. Stănescu A.D., Nistor E., Sajin M., Stepan A.E. Immunohistochemical analysis in the diagnosis of uterine myometrial smooth muscle tumors. Rom. J. Morphol. Embryol. 2014; 55 (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; 5: 7–1. https://doi.org/10.1186/1746-1596-7-1
  11. Czarkowska-Paczek B., Przybylski J. Mechanism of tissue repair. PrzLek. 2004; 61: 39–42.
  12. Jayes F.L., Liu B., Feng L., Aviles-Espinoza N., Leikin S., Leppert P.C. Evidence of biomechanical and collagen heterogeneity in uterine fibroids. PLoS One. 2019; 14 (4): e0215646. https://doi.org/10.1371/journal.pone.0215646.
  13. Jayes F.L., Liu B., Moutos F.T., Kuchibhatla M., Guilak F., Leppert P.C. Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase Clostridium histolyticum. Am. J. Obstet. Gynecol. 2016; 215 (5): 596.e1-596.e8. https://doi.org/10.1016/j.ajog.2016.05.006.
  14. Berto A.G., Sampaio, L.O., Franco, C.R., Cesar, R.M. Jr, and Michelacci, Y.M. A comparable analysis of structure and spatial distribution of decorin in human leiomyoma and normal myometrium. Biochimica Biophys Acta. 2003; 1619: 98–9112.
  15. Kalir T., Goldstein M., Dottino P., Brodman M., Gordon R., Deligdisch L. et al. Morphometric and electron-microscopic analysis of the effects of gonadotropin-releasing hormone agonists on uterine leiomyomas. Arch. Pathol. Lab. Med. 1998; 122: 442–6.
  16. Plewka D., Morek M., Bogunia E., Waloszek J., Plewka A. Expression of VEGF isoforms and their receptors in uterine myomas. Ginekol. Pol. 2016; 87 (3): 166-77. https://doi.org/10.17772/gp/60979