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Evaluation of EZH2 expression, BRAF V600E mutation, and CDKN2A/B deletions in epithelioid glioblastoma and anaplastic pleomorphic xanthoastrocytoma

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Abstract

Introduction

Epithelioid glioblastoma (EGBM) and anaplastic pleomorphic xanthoastrocytoma (APXA) are two rare entities with different prognoses. However, they share certain morphological and molecular features.

Materials and methods

To better recognize EGBM and APXA and identify the prognostic factors associated with these tumors, EZH2 status, BRAF V600E mutations, and CDKN2A/B deletions were assessed in 15 APXA and 13 EGBM cases.

Results

The expression level of EZH2 was found to increase with tumor grade. Overexpression of EZH2 occurred in 69.2% (9/13) of EGBM cases and 20% (3/15) of APXA cases. In addition, 72.7% (8/11) of EGBM and 12.5% (1/8) of APXA cases harbored a CDKN2A homozygous deletion based on fluorescence in situ hybridization. BRAF V600E mutations were detected in 80% (8/10) of EGBM cases and 42.9% (3/7) of APXA cases. Furthermore, EGBM, which exhibited co-existing low-grade glioma-like lesions, was found to have strong EZH2 expression and high Ki-67 indexes only in epithelioid cells and not in low grade lesions. Univariate analysis demonstrated that abundant epithelioid cells, extensive necrosis, EZH2 overexpression and BRAF V600E mutations were significantly associated with decreased overall survival in EGBM and APXA patients (P < 0.05).

Conclusions

The results suggested that testing for EZH2 expression and BRAF V600E mutations might be helpful to evaluate the prognoses of EGBM and APXA patients. The presence of heterogeneous EZH2 expression in biphasic EGBMs could also contribute to malignant progression.

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Funding

This work was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (grant Number 2013BAI09B03) and Beijing Institute for Brain Disorders (Grant Number BIBD-PXM2013_014226_07_000084).

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Authors and Affiliations

  1. Department of Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases (NCRC-ND), Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing Key Brain Tumor Laboratory, Beijing, China

    Junmei Wang, Zhaoxia Liu, Yun Cui, Jingyi Fang, Li Xu, Yanjiao He, Jiang Du, Yujin Su, Wanjing Zou, Zuolin Xu & Guilin Li

  2. Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases (NCRC-ND), Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing Key Brain Tumor Laboratory, Beijing, China

    Yuqing Liu

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  1. Junmei Wang
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Correspondence to Guilin Li.

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Wang, J., Liu, Z., Cui, Y. et al. Evaluation of EZH2 expression, BRAF V600E mutation, and CDKN2A/B deletions in epithelioid glioblastoma and anaplastic pleomorphic xanthoastrocytoma. J Neurooncol 144, 137–146 (2019). https://doi.org/10.1007/s11060-019-03212-0

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