PMID- 28631712 OWN - NLM STAT- MEDLINE DCOM- 20180426 LR - 20181023 IS - 0004-1955 (Print) IS - 0004-1955 (Linking) VI - 79 IP - 3 DP - 2017 TI - [The molecular mechanisms and morphological manifestations of leiomyoma reduction induced by selective progesterone receptor modulators]. PG - 19-26 LID - 10.17116/patol201779319-26 [doi] AB - AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-beta, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia. Group 1 included 40 patients who were treated with ulipristal for 3 months, followed by laparoscopic myomectomy. Group 2 consisted of 35 patients who underwent surgery without previous preparation. The intra- and postoperative parameters and molecular and morphological changes in the myomatous nodules were comparatively analyzed in both groups. RESULTS: After 3 months of therapy initiation, menorrhagia completely ceased, myomatous nodules decreased in size (p<0.05), hemoglobin levels were elevated (p<0.01), and total intraoperative blood loss and operative time decreased in all the patients in Group 1. The morphological substrate of partial leiomyoma reduction was leiomyocyte apoptosis and dystrophy, tumor stroma sclerosis and hyalinosis with diminished Ki-67 expression and elevated p16 in the smooth muscle cells, trophic nodular tissue disorders exhibited by vascular wall sclerosis and lower VEGF and TGF-beta expression, and leiomyocyte hormonal reception dysregulation that made itself evident through the reduced expression of SRC-1 with the unchanged expression of PR and ER and the maintained level of NCoR-1. CONCLUSION: The molecular mechanisms of tumor reduction involved the reduced Ki-67 expression and elevated p16, lower VEGF and TGF-beta, diminished SRC-1 expression with the maintained level of PR, ER, and NCoR-1. Overall, this is suggestive of enhanced apoptosis and reduced leiomyoma proliferation and angiogenesis induced by SPRM and indicative of the expediency of using ulipristal acetate as a preoperative agent for organ-sparing surgery in reproductive-aged patients with uterine myoma, menorrhagias, and anemia. FAU - Demura, T A AU - Demura TA AD - I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia. FAU - Revazova, Z V AU - Revazova ZV AD - Academician V.I. Kulakov Research Centre of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia. FAU - Kogan, E A AU - Kogan EA AD - I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia. FAU - Adamyan, L V AU - Adamyan LV AD - Academician V.I. Kulakov Research Centre of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia. LA - rus PT - Journal Article TT - Molekuliarnye mekhanizmy i morfologicheskie proiavleniia reduktsii leiomiomy pod vozdeistviem selektivnykh moduliatorov retseptorov progesterona. PL - Russia (Federation) TA - Arkh Patol JT - Arkhiv patologii JID - 0370604 RN - 0 (Biomarkers, Tumor) RN - 0 (Norpregnadienes) RN - 0 (Receptors, Progesterone) RN - YF7V70N02B (ulipristal acetate) SB - IM MH - Adult MH - Biomarkers, Tumor/*metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Leiomyoma/*drug therapy/metabolism/pathology MH - Norpregnadienes/administration & dosage/*therapeutic use MH - Receptors, Progesterone/*metabolism MH - Treatment Outcome MH - Uterine Myomectomy MH - Uterine Neoplasms/*drug therapy/metabolism/pathology OTO - NOTNLM OT - angiogenesis OT - apoptosis OT - menorrhagia OT - nuclear receptor corepressor 1 OT - progesterone OT - proliferation OT - steroid receptor coactivator-1 OT - ulipristal acetate OT - uterine myoma EDAT- 2017/06/21 06:00 MHDA- 2018/04/27 06:00 CRDT- 2017/06/21 06:00 PHST- 2017/06/21 06:00 [entrez] PHST- 2017/06/21 06:00 [pubmed] PHST- 2018/04/27 06:00 [medline] AID - 10.17116/patol201779319-26 [doi] PST - ppublish SO - Arkh Patol. 2017;79(3):19-26. doi: 10.17116/patol201779319-26.