Transmembrane estrogen receptor GPR30 is more frequently expressed in malignant than benign ovarian endometriotic cysts and correlates with MMP-9 expression.

OBJECTIVE

Molecular studies supporting the idea of malignant transformation of endometriosis are sparse and not well substantiated. The aims of this study were to detect expression levels of the novel estrogen-responsive receptor G protein-coupled estrogen receptor 1 GPER, also termed GPR30, and to determine its correlation with matrix metalloproteinase-9 (MMP-9) in benign and malignant ovarian endometriotic cysts and to explore the significance of GPR30.

METHODS

Immunohistochemical staining with the streptavidin-peroxidase method was conducted to determine the expression of GPR30 and MMP-9 in 24 cases of endometriosis-associated ovarian carcinoma (EAOC) and 32 specimens of ovarian endometriosis without malignant transformation. Reverse transcriptase polymerase chain reaction was performed to determine messenger RNA expression of GPR30 and MMP-9 in benign and malignant ovarian endometriotic cysts. We also investigated their associations with known clinic pathological parameters and the interrelationship between the expressions of the 2 proteins.

RESULTS

The positive staining ratio of GPR30 was 95.8% (23/24) in EAOC cases, and the HScore was 268; whereas the positive ratio was 25% (8/32) in benign endometriotic cysts, and the Hscore was 95. Matrix metalloproteinase-9 was expressed in all 24 EAOC cases and 87.5% (28/32) of the benign samples, and the Hscores were 280 and 260, respectively (P > 0.05). The receptor GPR30 was significantly higher in EAOCs than in benign endometriotic cysts (P < 0.05). The expression of GPR30 messenger RNA was also significantly higher in malignant ovarian endometriotic cysts than in the benign group. The receptor GPR30 was positively related to tumor size, tumor stage, and lymph node metastasis. A positive relationship between GPR30 and MMP-9 was found (P = 0.002).

CONCLUSIONS

The results suggest that the abnormal expression of GPR30 may be involved in malignant transformation, invasion, and metastasis of EAOCs. Testing of GPR30 expression levels may present both diagnostic and therapeutic options for the treatment of ovarian malignancies.