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促性腺激素释放激素(GnRH)及其在人脑膜瘤中的受体。

Gonadotropin-releasing hormone (GnRH) and its receptor in human meningiomas.

作者信息

Hirota Yuichi, Tachibana Osamu, Uchiyama Naoyuki, Hayashi Yasuhiko, Nakada Mitsutoshi, Kita Daisuke, Watanabe Takuya, Higashi Ryo, Hamada Jun-ichiro, Hayashi Yutaka

机构信息

Department of Neurosurgery, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Japan.

出版信息

Clin Neurol Neurosurg. 2009 Feb;111(2):127-33. doi: 10.1016/j.clineuro.2008.09.015. Epub 2008 Nov 2.

Abstract

OBJECTIVE

Meningiomas are the most common neoplasms of the central nervous system and are more frequent in women than in men. Many studies have been conducted to determine whether the progesterone receptor (PR) and estrogen receptor (ER) are present or absent in meningiomas. No previous studies, however, have investigated the status (presence or absence) of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R), two major factors related to PR and ER, in meningiomas. This study aims to determine the status of GnRH and GnRH-R and to elucidate the correlations of GnRH and GnRH-R with PR, ER, and clinical features in meningiomas.

METHODS

Eighty-two specimens of human meningiomas were obtained for immunohistochemical analysis with anti-GnRH, anti-GnRH-R, anti-PR, anti-ER, and anti-Ki-67 (MIB-1) antibodies, and for RT-PCR analysis of the mRNA expressions of GnRH and GnRH-R. Correlations of GnRH and GnRH-R with PR, ER, Ki-67, and clinical features such as age, sex, tumor grade, and tumor histology were assessed.

RESULTS

Seventy-eight (95.1%) of the 82 meningiomas reacted positively in the cytoplasm for the GnRH-R. Forty-nine (59.8%) of the 82 cases reacted positively in the cytoplasm for the GnRH. The positive immunoreactivity for GnRH-R and GnRH was confirmed by the RT-PCR analyses of mRNA. Forty-seven (96%) of the 49 cases with positive immunoreactivity for GnRH-R also had positive immunoreactivity for GnRH. PR expression was higher in the tumors positive for GnRH-R (p=0.002), and a significantly higher proportion of tumors from male patients exhibited positive immunoreactivity for GnRH (p=0.02). No significant correlations were found between the status of GnRH-R or GnRH with other clinicopathological features.

CONCLUSION

Over half of meningiomas may be regulated by GnRH-GnRH-R expression in an autocrine fashion. This unique expression profile of GnRH and GnRH-R may open the way to the development of GnRH analogs as a treatment tool in the future.

摘要

目的

脑膜瘤是中枢神经系统最常见的肿瘤,女性发病率高于男性。已有多项研究旨在确定脑膜瘤中是否存在孕激素受体(PR)和雌激素受体(ER)。然而,此前尚无研究调查脑膜瘤中促性腺激素释放激素(GnRH)及其受体(GnRH-R)这两个与PR和ER相关的主要因素的状态(存在或不存在)。本研究旨在确定GnRH和GnRH-R的状态,并阐明GnRH和GnRH-R与脑膜瘤中PR、ER及临床特征的相关性。

方法

获取82例人脑膜瘤标本,用抗GnRH、抗GnRH-R、抗PR、抗ER和抗Ki-67(MIB-1)抗体进行免疫组化分析,并对GnRH和GnRH-R的mRNA表达进行逆转录聚合酶链反应(RT-PCR)分析。评估GnRH和GnRH-R与PR、ER、Ki-67以及年龄、性别、肿瘤分级和肿瘤组织学等临床特征的相关性。

结果

82例脑膜瘤中有78例(95.1%)GnRH-R在细胞质中呈阳性反应。82例中有49例(59.8%)GnRH在细胞质中呈阳性反应。mRNA的RT-PCR分析证实了GnRH-R和GnRH的阳性免疫反应性。49例GnRH-R免疫反应阳性的病例中有47例(96%)GnRH也呈阳性免疫反应。GnRH-R阳性的肿瘤中PR表达更高(p=0.002),男性患者的肿瘤中GnRH呈阳性免疫反应的比例显著更高(p=0.02)。未发现GnRH-R或GnRH的状态与其他临床病理特征之间存在显著相关性。

结论

超过半数的脑膜瘤可能以自分泌方式受GnRH-GnRH-R表达的调节。GnRH和GnRH-R这种独特的表达谱可能为未来开发GnRH类似物作为治疗工具开辟道路。

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