Histomolecular characterization of intracranial meningiomas developed in patients exposed to high-dose cyproterone acetate: an antiandrogen treatment

Abstract

Background Meningiomas are the most common primary intracranial tumors in adults. The relationship between meningiomas and exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet the underlying mechanisms remain unknown. Defining the histomolecular status of meningiomas developed on CPA would help us to better understand the oncogenesis of these tumors. Methods We identified 30 patients operated for a meningioma after long-term high-dose CPA therapy and with a history of CPA discontinuation before establishing the indication for surgical intervention. We used array-comparative genomic hybridization (to characterize copy number changes in those 30 meningiomas and subsequently performed next-generation sequencing with the National Institute of Cancer (INCa) solid tumor panel, which is a targeted panel of clinically actionable genes. We also examined grade, type, and clinical features. Results We identified AKT1 mutations or PIK3CA mutations in 33.3% of CPA meningiomas. AKT1 and PIK3CA mutations were mutually exclusive. Enrichment in oncogenic PIK3CA mutations in the CPA cohort was detected. CPA meningiomas showed chromosomal stability and were located mainly in the skull base. Ninety percent of CPA meningiomas were low-grade meningiomas and 63.4% were meningotheliomas. Half of our CPA cohort had microcystic components. Conclusion Our study shows that low-grade meningothelial meningiomas of the skull base are predominant in CPA meningiomas. We identified PIK3CA/AKT1 pathway as a hypothetical actor in onco-pharmacological interaction between meningiomas and CPA. This signaling pathway could be an interesting target for precision medicine trials in meningioma patients who have been subjected to CPA. Our results could invite the scientific community to review the current classification of meningiomas and to evolve toward more specific histomolecular classification.

Atypical evolution of meningiomatosis after discontinuation of cyproterone acetate: clinical cases and histomolecular characterization

“…Concerning progestin-associated meningiomas which account for almost one third of the multiple meningioma, they seem to be characterized by a speci c mutational landscape. PIK3CA pathogenic mutations were identi ed in progestin-associated meningiomas in comparison with a control population [21,22]. This is the rst report of CPA related meningiomatosis with opposed evolution of meningiomas in the same patient after CPA discontinuation with regressing tumors while other meningiomas continued to growth.…”

“…CPA-related meningiomas also seem to be more often multiple and localized on the anterior or mid-skull base and the anterior convexity [21,22].It is well known that the meninges have different embryological origins [33] depending on the anatomical site; this embryological origin might be associated with the pathophysiology of various diseases such as meningiomas [26,34]. Recently, Okano et al [24] demonstrated that oncogenic mutations and meningioma characteristics (tumor location, histological ndings) are associated with meningeal origins.…”

“…Concerning the molecular standpoint, recent reports have shown that pathogenic PIK3CA/AKT1 mutations are more frequently foundin progestin-associated meningiomas [21,22]. Meningioma mutations affecting the PIK3CA/AKT1 pathway are also more frequent in skull base location whereas meningiomas arising from the convexity or the posterior fossa harbor mutations in theNF2-gene [21,[23][24][25].…”

Coexistence of craniopharyngioma and meningioma

“…[ 17 – 19 ] It is now well-documented that meningiomas have endogenous and exogenous sex hormonal susceptibility. [ 20 – 22 ] Three patients presented hormonal disorder, and 4 cases showed craniopharyngioma of adamantinomatous type. The meningioma showed different types.…”

Raman imaging and statistical methods for analysis various type of human brain tumor

“…Meningotheliomas are the most frequent brain tumors in adults and they occur more often in female than in male. 6 When meningotheliomas are in benign stadium they carry a good prognosis. Standard treatment for meningotheliomas is surgical resection.…”