Dysregulation of Apoptosis Caused by Aberrant Histone Modification Influences on the Recurrence of Meningiomas

Young Zoon Kim

doi:10.21767/2472-1158.100083

Abstract

Background: Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study was aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. Materials and method: The medical records of 67 patients with AMs, as diagnosed during recent 13 years, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Results: Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than underexpression, and overexpression of Survivin, MDM2, and BCL2 had a shorter TTR than underexpression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than underexpression, and overexpression of KDM5c had a longer TTR than underexpression. However, in the multi-variate analysis of predicting factors for recurrence, underexpression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusion: This study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.

Highlights

Atypical meningiomas (AMs) are reported to account for 20%–35% of all meningiomas; they represent an intermediate subtype between benign and anaplastic meningiomas in the World Health Organization (WHO) classification [1,2,3,4]
This study suggests certain apoptosis-associated factors should be associated with recurrence of atypical meningiomas (AMs), which may be regulated epigenetically by histone modifying enzymes
Overexpression of survivin and BCL2 and underexpression CASP3 and BAX were associated with high recurrence rate in AMs, which was concordant with previous reports

Summary

Introduction

Atypical meningiomas (AMs) are reported to account for 20%–35% of all meningiomas; they represent an intermediate subtype between benign and anaplastic meningiomas in the World Health Organization (WHO) classification [1,2,3,4]. Benign meningiomas are generally slow growing and have a low recurrence rate after gross total resection (GTR) [5,6]. AMs are more locally aggressive and demonstrate more rapid tumor progression. AMs are associated with significantly increased mortality. Because of their aggressive behavior, AMs have an unpredictable outcome, and reported. Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). This study was aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs

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Conclusion