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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.

SUBMITTER: Portet S

PROVIDER: S-EPMC7212922 | biostudies-literature | 2019 May-Dec

REPOSITORIES: biostudies-literature

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

Portet Sylvain S Naoufal Rania R Tachon Gaëlle G Simonneau Adrien A Chalant Anaïs A Naar Amir A Milin Serge S Bataille Benoit B Karayan-Tapon Lucie L

Neuro-oncology advances 20190528 1

<h4>Background</h4>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.<h4>Methods</h4>We identified 30 patients operated for a meningioma after long-term high-dose CPA therapy and wi ...[more]

PMID: 32642646

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Project description:Cyproterone acetate 2 mg/ethinylestradiol 35 µg, an estrogen/progestogen treatment with anti-androgenic properties, shares a thromboembolism risk with combined hormonal contraceptives. Educational materials (i.e., direct healthcare professional communication, patient information card, prescriber checklist) were distributed to physicians to increase risk awareness.The objective of this study was to measure physician knowledge of thromboembolism risk of cyproterone acetate 2 mg/ethinylestradiol 35 µg and ascertain whether physicians received the educational materials.A cross-sectional web-based physician survey of recent prescribers of cyproterone acetate 2 mg/ethinylestradiol 35 µg in Austria, the Czech Republic, France, the Netherlands, and Spain was conducted. Sampling targets for physician specialty were based on country-specific prescribing patterns. Frequency of correct responses was calculated for 14 knowledge questions.Among 759 physician respondents (37% of obstetricians/gynecologists, 42% of general practitioners, 20% of dermatologists), 51% received one or more of three educational materials. Knowledge was highest (?80%) for symptoms of possible deep vein thrombosis, pulmonary embolism, and cerebrovascular accident; most important risk factors for thrombosis; use in smokers; indication for moderate-to-severe acne; and understanding that cyproterone acetate 2 mg/ethinylestradiol 35 µg should not be used for contraception alone. Knowledge varied for contraindications, myocardial infarction symptoms, other risk factors for thrombosis, instructions regarding anticipated prolonged immobilization, and selected concomitant medical conditions. Knowledge was lower regarding prescribing cyproterone acetate 2 mg/ethinylestradiol 35 µg for acne only after failure of topical therapy or systemic antibiotics. Generally, knowledge did not vary by physician specialty, receipt of educational materials, number of patients prescribed cyproterone acetate 2 mg/ethinylestradiol 35 µg in the previous 3 months, and years in practice.Knowledge was generally high for thromboembolism risk and varied for more complex or infrequent topics.

Dataset Information

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

Publications

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

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