High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients

Lisa Stefanie Hönikl,Jens Gempt,Claire Delbridge,Friederike Lämmer,Jürgen Schlegel,Bernhard Meyer

doi:10.1007/s11060-020-03467-y

Lisa Stefanie Hönikl, Jens Gempt + Show 4 more

Open Access

https://doi.org/10.1007/s11060-020-03467-y

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Abstract

IntroductionGlioblastoma 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.Methods60 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.ResultsHigh 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.ConclusionERα-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.

Highlights

Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women
When GBM cells were transplanted into athymic mice [11] or nude rats [12] the tumor growth was higher in male than female animals, indicating that sexual hormones have a decisive influence on tumor proliferation
For further classifications 0–40% of immune positive stained tumor cells was rated as low expression of the hormones and 41–100% was classified as high expression

Summary

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 to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro. 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. When GBM cells were transplanted into athymic mice [11] or nude rats [12] the tumor growth was higher in male than female animals, indicating that sexual hormones have a decisive influence on tumor proliferation

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