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.

Chinese abstract

雌激素α受体和孕激素受体在未接受治疗和接受不同治疗方案的深部浸润型子宫内膜异位症患者中存在表达差异性

摘要

深部浸润型子宫内膜异位症（DIE）对于激素治疗的反应有别于其他类型。现已在一部分子宫内膜异位上皮细胞中发现突变的癌症驱动基因, 提示病变部位可能存在功能异质性。本研究为评估深部浸润型子宫内膜异位症的细胞表型异质性, 分别检测未受治疗和进行不同治疗方案的DIE患者病变组织的雌激素α受体（ERα）和孕激素受体（PR）表达水平, 并对不同组织的腔上皮高度（LEH）、免疫反应评分（IRS）及基质染色强度（SSI）进行分析。研究发现, 在同一腺体、同一组织样品中的不同腺体和接受相同治疗的不同患者中, 均出现高变异性。同一腺体中的上皮细胞异质性是造成LEH差异的最主要原因, 其次是由于对同一病变部位不同腺体的随机评估性造成, 第三则归因于患者的处理因素不同。同一患者中IRS和SSI的差异主要是细胞表达异质性的结果。LEH和SSI结果与患者的治疗方案无关。已进行治疗患者中PR表达阳性组织的IRS水平在较低。ERα和PR分布的异质性可能造成激素治疗对该病疗效不佳。

关键词: 深部浸润型子宫内膜异位症, 雌激素受体, 孕激素受体

Keywords:

• Deep infiltrating endometriosis
• estrogen receptor
• progesterone receptor

Acknowledgements

We would like to thank Isabelle Dasoul and Emilie Feyereisen for their technical advices.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Fonds De La Recherche Scientifique – FNRS (F.R.S.-FNRS, Belgium), grant number 1.1.394.09.