Heterogeneity of estrogen receptor α and progesterone receptor distribution in lesions of deep infiltrating endometriosis of untreated women or during exposure to various hormonal treatments

Abstract

Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a functional heterogeneity of these lesions. To evaluate the phenotype heterogeneity of cells in DIE, we measured the expression of estrogen receptor α (ERα) and of progesterone receptor (PR) in DIE of untreated women or under various treatments. We analyzed the luminal epithelial height (LEH), immunoreactive epithelial staining (IRS) and stromal staining intensity (SSI) of ERα and PR. We observed a high variability in the same gland, among distinct glands in the same sample and among distinct patients receiving the same treatment. LEH variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomly evaluated on the same section, and tertiary to the patient category. Variability in IRS and SSI scores was primarily the consequence of their heterogeneity in the same woman and to a lesser extent to variability among patients. LEH and SSI were not modified according to treatment. IRS for PR was lower in treated patients. This heterogeneity of ERα and PR distribution could explain why endocrine treatments are unable to cure this condition.

Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment

“…Nisolle et al . 24 found “heterogeneity of estrogen receptor α and progesterone receptor distribution in lesions of DIE in untreated women, or during exposure to various hormonal treatments”. This could be because DIE nodules are poor responders to different endocrine treatments.…”

Potential Therapeutic Options and Perspectives for Alleviation of Endometrial Estrogen Dominance and Progesterone Resistance in Endometriosis

“…A recent European study on deep endometriosis [64] showed a high variability of ERα and PR distribution in the same gland, among distinct glands of the same sample, and among distinct patients receiving the same treatment. Luminal epithelial height variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomaly evaluated on the same section, and tertiary to the patient category.…”

New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments

“…Targeting specific DIE features, such as fibrosis, is of interest in future treatment research [ 16 , 17 ]. The heterogeneity of the ER-α and PR distribution could explain why endocrine treatments are unable to cure this condition and allow us to only stop progression [ 5 ]. Recently, androgen receptors (ARs) were evaluated in stromal and epithelial cells with a higher density in the former than in the latter [ 18 ].…”

“…We showed in a retrospective cross-sectional study that women with deep infiltrating endometriosis either undergoing a different hormonal treatment or untreated presented a large intra-lesion, intra-patient, and intra-treatment variance in the expression levels of ERs, which was more evident than any difference between treatments or between treated and non-treated lesions [ 5 ]. This heterogeneity in the ER-α and PR distribution could explain why endocrine treatments are unable to cure this condition and allow us to only stop progression.…”

“…To date, no optimal medical treatment for endometriosis can be proposed as it frequently fails. The heterogeneity of the distribution of estrogen receptors (ERs) and progesterone receptors (PRs) of the lesions described by Brichant et al could be the explanation for these results [ 5 ]. The development of new biological targets is urgently needed.…”