Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Gynecol Obstet Invest. 2018;83(5):443-454. doi: 10.1159/000480011. Epub 2017 Dec 11.

Abstract

Objective: To investigate whether ulipristal acetate (UPA) treatment modifies the expression of progesterone receptor (PR), its nuclear cofactors steroid receptor coactivator-1 (SRC1) and nuclear corepressor-1 (NCoR1), prosurvival factor B-cell lymphoma 2 (Bcl-2), and Akt in uterine myomas.

Patients: Prospective study of 59 women with symptomatic myomas undergoing myomectomy. Forty-two patients were treated preoperatively with UPA; the remaining 17 were not and they served as controls.

Method: Tissue microarrays were obtained from surgical specimens and immunohistochemistry was performed. Blinded quantification of expression of PR (PR-A vs. PR-B), coactivator SRC1 and corepressor NCoR1, and prosurvival factor Bcl-2, and Akt and evaluation of Akt phosphorylation levels.

Results: Compared with the control group, UPA does not alter PR protein levels or expression patterns in myomas, and the PR-A/PR-B ratio was similar, as well as cytoplasmic or nuclear expression of cofactors SRC1 and NCoR1. Bcl-2 was heterogeneously expressed throughout the samples and no significant modification in expression was evidenced. No significant difference was found in Akt expression and phosphorylation between treated and untreated myomas.

Conclusion: This study did not find any significant change in the expression of the studied factors in myomas after UPA exposure. In conclusion, various theories on myomas cells proposed on the basis of in vitro studies are not supported in vivo.

Keywords: Progesterone receptor; Akt; Bcl-2; Immunohistochemistry; Nuclear cofactors; Ulipristal acetate; Uterine myoma.

MeSH terms

  • Adult
  • Case-Control Studies
  • Co-Repressor Proteins
  • Female
  • Humans
  • Leiomyoma / drug therapy
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Norpregnadienes / therapeutic use
  • Nuclear Receptor Coactivator 1 / metabolism*
  • Phosphorylation
  • Prospective Studies
  • Protein Isoforms
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptors, Progesterone / metabolism*
  • Receptors, Progesterone / therapeutic use
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • Co-Repressor Proteins
  • Norpregnadienes
  • Protein Isoforms
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Progesterone
  • progesterone receptor B
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1
  • Proto-Oncogene Proteins c-akt
  • ulipristal acetate