The immunohistochemical expression of GPER and classical sex hormone receptors differs in adenomyosis and eutopic endometrium

G protein-coupled estrogen receptor (GPER) has been found to be an important key regulator in the homeostasis of sex hormone-dependent human cells. The aim of this study was to compare the expression of GPER, estrogen receptor alpha (ER-α), estrogen receptor beta (ER-β) and progesterone receptor (PR) in adenomyosis, eutopic endometrium from the same patients, and eutopic endometrium from patients without adenomyosis. Immunohistochemical analysis of GPER, ER-α, ER-β and PR was performed to assess the expression levels on samples of hysterectomies using tissue microarrays. 73 adenomyotic tissue probes and corresponding eutopic endometrial specimens, as well as 48 samples of eutopic endometrial control specimens from patients without adenomyosis were included in this study. Mean age of the women with adenomyosis was 51.7 (SD ± 11.1) and 65.8% were premenopausal. We found a higher nuclear stromal expression of GPER in eutopic endometrium of patients with adenomyosis in comparison to control endometrium (p < 0.001). Comparing adenomyosis to eutopic endometrium of patients with adenomyosis and to control, there was a lower expression of nuclear GPER in epithelial cells (p < 0.001 and p = 0.048, respectively). Lower epithelial nuclear ER-α in adenomyosis and higher epithelial nuclear ER-β in eutopic endometrium of patients with adenomyosis was found in comparison to control endometrium (p = 0.008 and p = 0.017, respectively). This study showed a significant difference in the immunohistochemical expression of GPER in adenomyosis compared to eutopic endometrium of the same patients and to endometrium of control group. GPER in adenomyosis may be a potential therapeutic target for selective agonists and antagonists.