RESUMO
INTRODUCTION: Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents. METHODS: Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8-110), and fluorescent and chromogenic in situ hybridization (n = 5-70) to determine mutational and expression status. RESULTS: The median age of patients in the cohort was 60 years, with a range spanning 6-90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%). CONCLUSION: If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.
Assuntos
Ensaios Clínicos como Assunto/métodos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/metabolismo , Meningioma/tratamento farmacológico , Meningioma/metabolismo , Projetos de Pesquisa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/patologia , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Adulto JovemAssuntos
Carcinoma Adenoide Cístico/classificação , Neoplasias Oculares/classificação , Doenças do Aparelho Lacrimal/classificação , Estadiamento de Neoplasias/normas , Adulto , Idoso , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/terapia , Criança , Neoplasias Oculares/patologia , Neoplasias Oculares/terapia , Feminino , Humanos , Doenças do Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/terapia , Masculino , Pessoa de Meia-Idade , Exenteração Orbitária , Prognóstico , Radioterapia Adjuvante , Reprodutibilidade dos Testes , Estados Unidos , Adulto JovemRESUMO
A 63-year-old woman had a diffuse uveal melanoma with massive extension in the orbit and optic chiasm. She received palliative radiation therapy. The importance of careful inspection of the enucleated specimen and postenucleation imaging studies to delineate the extent of the uveal tumor are underscored in this case. Treatment options may include skull base surgery or palliative radiotherapy.