Sex-specific differences in meningioma subtypes and mutations - a retrospective analysis

Abstract A variety of intrinsic and extrinsic factors are known to influence and promote the development of cancer. Although the patients’ gender can influence extrinsic factors, biological sex is an important intrinsic factor. Here, it must also be considered that hormone levels change over the lives of patients. To further investigate these aspects, meningioma can serve as a prototype tumor. Differences are already obvious when analyzing the epidemiology and outcomes: Females are more frequently diagnosed with meningioma, but high-grade meningiomas and fatal outcomes are more frequently observed in males. To further resolve sex and potentially hormone-specific differences, we retrospectively examined a dataset of 798 patients (females n=541, males n=257). Additionally, we arbitrarily set a cut-off of 58 years to stratify for females between pre- and post-menopause. The male cohort was analyzed accordingly to exclude an age-dependent effect. Further, the female cohort was subdivided into “45-55 years” and “other” to analyze the impact of high hormone fluctuations within menopause. When examining the histological data, we found that women displayed the chordoid subtype more frequently than men (6.3% vs. 1.6%). In the age-dependent analyses, there may be a signal for a hormone-dependent effect, as for females this subtype was diagnosed more frequently < 58 than > 58 years of age (10.6% vs. 1.9%; males: 0% vs. 3.0%) and within the menopause (15.5% vs. 3.2%). The same pattern was noted for the TRAF7 mutation, which was detected more frequently in females (20.2% vs. 7.7%), females < 58 years (23.9% vs. 15.6%, males: 6.2% vs. 9.1%) and females within the menopause (27.9% vs. 17.6%) than in the respective other subgroups. This preliminary data warrants further research in larger, comprehensively annotated cohorts and analysis for hormone levels and receptor expression.