Colón-Caraballo Mariano, García Miosotis, Mendoza Adalberto, Flores Idhaliz
Departments of Basic Sciences, Microbiology Division.
Hato Rey Pathology Inc., San Juan, PR.
Appl Immunohistochem Mol Morphol. 2019 Aug;27(7):491-500. doi: 10.1097/PAI.0000000000000663.
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.
大多数现有的子宫内膜异位症治疗方法都是基于激素的，并且通常在不考虑卵巢激素受体表达状态的情况下广泛使用。这与其他基于激素的疾病（如乳腺癌）的治疗标准形成了鲜明对比。因此，我们旨在使用组织微阵列（TMA）来表征雌激素α（ESR1）、雌激素β（ESR2）和孕激素（PGR）在不同类型的子宫内膜异位症病变以及子宫内膜异位症患者和对照者的在位内膜中的表达情况。通过组织（即异位内膜与在位内膜）和细胞类型（即腺体与间质）分析受体的核表达水平。卵巢病变显示ESR1和PGR的表达最低，ESR2的表达最高，而输卵管病变显示这三种受体的高表达。内膜之间的差异包括患者增殖期内膜间质中ESR1表达较低而ESR2表达较高，以及患者增殖期内膜中PGR核阳性丧失的趋势。在卵巢病变和分泌期内膜中观察到最大的ESR2:ESR1比值。Ki67阳性细胞核>10%的样本比例最高的是输卵管腺体（54%）和盆腔外病变（75%）；患者分泌期内膜腺体中有60%的Ki67阳性率>10%，而对照中只有15%。我们的结果通过揭示卵巢激素受体表达的病变类型特异性差异和个体差异，更好地理解了子宫内膜异位症的异质性。这些知识可能有助于预测个体对激素治疗的反应，并为子宫内膜异位症患者应用个性化医疗方法奠定基础。
