Human TERT Promoter Mutations in Atypical and Anaplastic Meningiomas.

Marta Mellai,Renzo Boldorini,Marco Krengli,Valentina Fogazzi,Aurora Mustaccia,Omar Porrini Prandini,Marta Allesina

doi:10.3390/diagnostics11091624

Abstract

Background: The role of telomerase reverse transcriptase (TERT) gene promoter mutations (pTERT) in atypical and anaplastic meningiomas remains controversial. This study aimed to evaluate their impact on the histologic diagnosis and prognosis in a retrospective series of 74 patients with atypical and anaplastic meningioma, including disease progression and relapse. A supplementary panel of 21 benign tumours was used as a control cohort. Materials and Methods: The mutation rate of the pTERT gene was assessed by Sanger sequencing. ATRX protein expression was detected by immunohistochemistry. The phenotypic and genotypic intra-tumour heterogeneity was studied in a sub-group of 12 cases using a Molecular Machines & Industries (MMI) CellCut laser microdissection (LMD) system. Results: pTERT mutations were detected in 12/74 (17.6%) malignant meningiomas. The mutation rate was significantly higher in anaplastic meningiomas (7/23, 30.4%) compared to atypical tumours (5/48, 10.4%) (p = 0.0443). In contrast, the mutation rate was < 5% in benign tumours. All pTERT mutant cases retained nuclear ATRX immunoreactivity. pTERT mutations were significantly associated with the histologic grade (p = 0.0443) and were adverse prognostic factors for anaplastic tumours (p = 0.06). Conclusion: We reported on the pTERT mutation spectrum in malignant meningiomas, supporting their use in the prognostic classification.

Highlights

Meningiomas are the most common primary tumours of the central nervous system (CNS) [1]
This study aimed to evaluate their impact on the histologic diagnosis and prognosis in a retrospective series of 74 patients with atypical and anaplastic meningioma, including disease progression and relapse
We reported on the promoter mutations (pTERT) mutation spectrum in malignant meningiomas, supporting their use in the prognostic classification

Summary

Introduction

Meningiomas are the most common primary tumours of the central nervous system (CNS) [1]. Grade II (atypical) meningiomas are classified as an intermediate grade between benign and malignant forms. They comprise atypical, clear cells and chordoid morphologic variants and show increased mitotic activity (with ≥4 mitoses per 10 HPF), brain infiltration or ≥3 of the histopathologic features associated with atypia (increased cellularity, small cell areas with a high nucleus-cytoplasm ratio, prominent nucleoli, sheet-like growth, and foci of spontaneous necrosis) [1]. The mutation rate was significantly higher in anaplastic meningiomas (7/23, 30.4%) compared to atypical tumours (5/48, 10.4%) (p = 0.0443). PTERT mutations were significantly associated with the histologic grade (p = 0.0443) and were adverse prognostic factors for anaplastic tumours (p = 0.06). Conclusion: We reported on the pTERT mutation spectrum in malignant meningiomas, supporting their use in the prognostic classification

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Methods

Conclusion