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Human Endometriosis Tissue Microarray Reveals Site-specific Expression of Estrogen Receptors, Progesterone Receptor, and Ki67

Colón-Caraballo, Mariano PhD*; García, Miosotis MD; Mendoza, Adalberto MD‡,§; Flores, Idhaliz PhD*,∥

Applied Immunohistochemistry & Molecular Morphology: August 2019 - Volume 27 - Issue 7 - p 491–500
doi: 10.1097/PAI.0000000000000663
Research Articles
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Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA). Nuclear expression levels of the receptors were analyzed by tissue (ie, ectopic vs. eutopic endometrium) and cell type (ie, glands vs. stroma). Ovarian lesions showed the lowest expression of ESR1 and PGR, and the highest expression of ESR2, whereas the fallopian tube lesions showed high expression of the 3 receptors. Differences among endometria included lower expression of ESR1 and higher expression of ESR2 in stroma of proliferative endometrium from patients versus patients, and a trend towards loss of PGR nuclear positivity in proliferative endometrium from patients. The largest ESR2:ESR1 ratios were observed in ovarian lesions and secretory endometrium. The highest proportion of samples with >10% Ki67 positive nuclei was in glands of fallopian tube (54%) and extrapelvic lesions (75%); 60% of glands of secretory endometrium from patients had >10% Ki67 positivity compared with only 15% in controls. Our results provide a better understanding of endometriosis heterogeneity by revealing lesion type-specific differences and case-by-case variability in the expression of ovarian hormone receptors. This knowledge could potentially predict individual responses to hormone therapies, and set the basis for the application of personalized medicine approaches for women with endometriosis.

Departments of *Basic Sciences, Microbiology Division

Pathology Division

Ob-Gyn, Ponce Health Sciences University

§Southern Pathology Inc., Ponce

Hato Rey Pathology Inc., San Juan, PR

Supported in part by NIH-NICHD grant number R01-HD050559 to IF; NIH-NIGMS grant number R25-GM082406 to MCC; and NIH-NCI grant number U56CA126379. This work was also supported by the PhD Program in Biomedical Sciences of the Ponce Health Sciences University.

M.C.C. and I.F.: performed experimental design, data collection, interpretation, and statistical analysis; drafted the manuscript. M.G. and A.M.: performed selection and pathologic analysis of the samples in the TMA. I.F. and M.C.C.: final approval of the manuscript.

The authors declare no conflict of interest.

Reprints: Idhaliz Flores, PhD, Department of Basic Sciences-Microbiology Division, Department of Obstetrics-Gynecology, Ponce Health Sciences University, Endometriosis Research Laboratory, Ponce Research Institute, 395 Calle Luis F. Salas, Ponce, PR 00716-2348 (e-mail: iflores@psm.edu).

Received July 7, 2017

Accepted February 28, 2018

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