Department of Obstetrics and Gynecology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Int J Gynecol Cancer. 2012 May;22(4):539-45. doi: 10.1097/IGC.0b013e318247323d.
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.
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.
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).
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.
支持子宫内膜异位症恶性转化观点的分子研究很少，且没有得到很好的证实。本研究旨在检测新型雌激素反应受体 G 蛋白偶联雌激素受体 1（也称为 GPR30）在良性和恶性卵巢子宫内膜异位症囊肿中的表达水平，并确定其与基质金属蛋白酶-9（MMP-9）的相关性，以探讨 GPR30 的意义。
采用链霉亲和素-过氧化物酶法进行免疫组织化学染色，检测 24 例卵巢子宫内膜癌相关癌（EAOC）和 32 例无恶性转化的卵巢子宫内膜异位症标本中 GPR30 和 MMP-9 的表达。采用逆转录聚合酶链反应检测良性和恶性卵巢子宫内膜异位症囊肿中 GPR30 和 MMP-9 的信使 RNA 表达。我们还研究了它们与已知临床病理参数的关系以及 2 种蛋白表达之间的相互关系。
在 EAOC 病例中，GPR30 的阳性染色率为 95.8%（23/24），H 评分 268；而良性子宫内膜异位症囊肿的阳性率为 25%（8/32），H 评分 95。基质金属蛋白酶-9 在 24 例 EAOC 病例和 87.5%（28/32）良性样本中均有表达，H 评分分别为 280 和 260（P > 0.05）。受体 GPR30 在 EAOC 中明显高于良性子宫内膜异位症囊肿（P < 0.05）。恶性卵巢子宫内膜异位症囊肿中 GPR30 信使 RNA 的表达也明显高于良性组。受体 GPR30 与肿瘤大小、肿瘤分期和淋巴结转移呈正相关。发现 GPR30 与 MMP-9 之间存在正相关关系（P = 0.002）。
结果表明，GPR30 的异常表达可能参与了 EAOC 的恶性转化、侵袭和转移。检测 GPR30 表达水平可能为卵巢恶性肿瘤的治疗提供诊断和治疗选择。
