Transmembrane Estrogen Receptor GPR30 is More Frequently Expressed in Malignant Than Benign Ovarian Endometriotic Cysts and Correlates With MMP-9 Expression

Li Long, Long L, Cao Y, Yi Cao, Liangdan Tang, Tang LD, Liang-Dan Tang
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2012 · vol. 22(4) , pp. 539–545 · doi:10.1097/igc.0b013e318247323d · PMID:22495744 · W2315994087
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The transmembrane estrogen receptor GPR30 is found more often in malignant ovarian endometriotic cysts compared to benign ones, and its presence correlates with MMP-9 expression.

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Abstract

ObjectiveMolecular 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.MethodsImmunohistochemical 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.ResultsThe 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).ConclusionsThe 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.

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Condition tags

endometriosis

MeSH descriptors

Biomarkers, Tumor Endometriosis Endometrium Matrix Metalloproteinase 9 Ovarian Cysts Ovarian Neoplasms Receptors, Estrogen Receptors, G-Protein-Coupled Biomarkers, Tumor Biomarkers, Tumor Endometriosis Endometriosis Endometriosis Endometrium Female Humans Immunoenzyme Techniques Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Middle Aged

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