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.

Although the histone methyltransferase EZH2 and its product H3K27me3 are well studied in cancer, little is known about their role and potential as therapeutic targets in endometriosis. We have previously reported that endometriotic lesions are characterized by global enrichment of H3K27me3. Therefore, we aimed to (1) characterize the expression levels of EZH2 in endometriotic tissues; (2) assess H3K27me3 enrichment in candidate genes promoter regions; and (3) determine if pharmacological inhibition of EZH2 impacts migration, proliferation, and invasion of endometriotic cells. Immunohistochemistry of an endometriosis-focused tissue microarray was used to assess the EZH2 protein levels in tissues. Chromatin immunoprecipitation-qPCR was conducted to assess enrichment of H3K27me3 in candidate gene promoter regions in tissues. Immunofluorescence was performed to assess the effect of an EZH2-specific pharmacological inhibitor on H3K27me3 global enrichment in cell lines. To measure effects of the inhibitor in migration, proliferation, and invasion in vitro we used Scratch, BrdU, and Matrigel assays, respectively. Endometriotic lesions had significantly higher EZH2α nuclear immunostaining levels compared to eutopic endometrium from patients (glands, stroma) and controls (glands). H3K27me3 was enriched within promoter regions of candidate genes in some but not all of the endometriotic lesions. Inhibition of EZH2 reduced H3K27me3 levels in the endometriotic cells specifically, and also reduced migration, proliferation but not invasion of endometriotic epithelial cells (12Z). These findings support future preclinical studies to determine in vivo efficacy of EZH2 inhibitors as promising nonhormonal treatments for endometriosis, still an incurable gynecological disease.

BackgroundPrevious epidemiological studies aimed at describing characteristics of breast (BC) and ovarian cancer (OC) patients tend to examine Hispanic populations using a mix of individuals that come from ethnically different Hispanic backgrounds. Since most USA cancer statistics do not include cancer data from Puerto Rico (PR), there is a lack of historical and descriptive data analysis for Hispanic women in the island that suffer from these diseases. Therefore, the aim of our study is to provide a comprehensive clinicopathological characterization of BC and OC cases in PR.MethodsOur study consisted of a longitudinal retrospective review of archived pathology reports at Southern Pathology Services (SPS), which mostly serves southwestern PR, from years 2000–2015. After filtering SPS records with pre-established criteria, tumor samples from 3451 BC and 170 OC cases were used for descriptive statistics and analysis using R program.ResultsIn our cohort, the mean age of diagnosis for BC was 60.5 years and 60.3 years for OC. Available data for subtype characterization from BC cases, exhibited an expected subtype distribution that remained stable over time (Luminal A = 68.8%, Luminal B = 9.7%, HER-2 = 6.1% and Triple negative = 15.4%). Additionally, tumor grades distribution varied within different BC subtypes in which the majority of Luminal A tumors were G2 and most Triple negative tumors were G3. For OC cases, available subtype and tumor grade information identified serous histology in 64.71% of all cases and G3 as being the most prevalent tumor grade. Pathology reports revealed that 39.42% of all OC cases were described as late stage, while 50.5% as early stage (by pathological staging).ConclusionOur data suggests that OC and BC subtypes distribution in Hispanic populations from PR are in-line with national averages. In a significant number of BC cases, subtype could not be determined due to study limitations, health insurance coverage, or other reasons described here and may constitute a health disparity. Altogether, and despite these gaps, this study represents one of the most complete reviews of BC and OC in PR and provides an opportunity to further study this population separate from other US Hispanic populations.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5077-z) contains supplementary material, which is available to authorized users.

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