Introduction

Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear, raising the question whether these effects are subject to hormonal control. The purpose of this study was to examine the expression of estrogen receptor alpha (ERα) and aromatase in human GBM tissue samples in relation to patient survival and furthermore to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro.

Methods

60 tissue samples (31 male, 29 female) of GBM patients were analysed with immunohistochemistry for ERα and aromatase for survival analyses. The cell lines LN18 and LN229 were treated with 17β-estradiol (E2) in different dosing regimens and the cell viability was measured with MTT assay. After estradiol pre-treatment Temozolomide was added and tested again.

Results

High expression of ERα and aromatase in the GBM tissue samples was associated with significantly longer survival times of GBM patients, regardless of gender and body-mass-index. The treatment with high concentrations of estradiol resulted in lower tumor cell viability, compared to control. The cells significantly showed a stronger sensitivity against Temozolomid (TMZ) after estradiol pre-treatment.

Conclusion

ERα-expression of glial tumour cells seems to play an important prognostic role as a biomarker in GBM, as well as the expression of the enzyme Aromatase. The combined treatment of GBM with standard chemotherapy and estradiol may be beneficial to patient’s survival.

中文翻译：

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在胶质母细胞瘤患者中，雌激素受体α和芳香化酶在神经胶质瘤细胞中的高表达与性别独立的生存获益有关。

介绍

多形胶质母细胞瘤（GBM）是一种高度恶性的神经胶质瘤，对男性的影响要比女性多。这种性别占主导地位的原因尚不清楚，这引起了这些影响是否受到激素控制的问题。这项研究的目的是检查与患者生存有关的人GBM组织样品中雌激素受体α（ERα）和芳香化酶的表达，并探讨标准化学疗法与雌二醇联合治疗对胶质母细胞瘤肿瘤细胞系的体外作用。

方法

用免疫组织化学方法对60例GBM患者的组织样品（男31例，女29例）进行了ERα免疫组化分析和芳香化酶分析，以进行生存分析。LN18和LN229细胞系在不同的给药方案下分别用17β-雌二醇（E2）处理，并通过MTT法测量细胞活力。雌二醇预处理后，加入替莫唑胺并再次测试。

结果

无论性别和身体质量指数如何，GBM组织样品中高表达的ERα和芳香化酶与GBM患者的生存时间明显延长有关。与对照相比，用高浓度的雌二醇处理导致较低的肿瘤细胞生存力。雌二醇预处理后，细胞明显显示出对替莫唑胺（TMZ）的更强敏感性。

结论

胶质瘤细胞的ERα表达似乎是GBM中生物标志物以及芳香酶的表达的重要预后作用。GBM与标准化学疗法和雌二醇的联合治疗可能有益于患者的生存。