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

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.

Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue

“…This indicated that the decline in the primordial follicle pool is due to two events, follicle activation and growth on the one hand, and follicle death on the other, both concurring and contributing to the burnout effect. In that study, we also found enhanced Akt phosphorylation in human primordial follicles 3 days after ovarian tissue transplantation, and can therefore infer that this could be a direct consequence of the hypoxic window that characterizes the immediate post-grafting period [3,4,[23][24][25][26].…”

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

“…(a) proteins that control the cell cycle and have a direct influence on the dynamics of proliferation, e.g., p16 [32,33,34]; cyclin D1 [35,36]; Bcl-2 [37]; proliferating cell nuclear antigen (PCNA) [38];…”

Ulipristal acetate for the management of large uterine fibroids associated with heavy bleeding: a review

“…Sustained fibroid shrinkage observed even after treatment cessation might therefore be the result of permanent ECM reduction. In the context of uterine fibroids, UPA does not alter expression patterns of progesterone receptors, nor their cofactors (Courtoy et al, 2017), indicating that the molecular mechanisms involved could be more complex than presumed. with high selectivity and affinity.…”