Junmei Wang1, Zhaoxia Liu1, Yun Cui1, Yuqing Liu2, Jingyi Fang1, Li Xu1, Yanjiao He1, Jiang Du1, Yujin Su1, Wanjing Zou1, Zuolin Xu1, Guilin Li3. 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. 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. 3. 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. liguilin2010@sina.com.
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.
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, BRAFV600E 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. BRAFV600E 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 BRAFV600E mutations were significantly associated with decreased overall survival in EGBM and APXApatients (P < 0.05). CONCLUSIONS: The results suggested that testing for EZH2 expression and BRAFV600E mutations might be helpful to evaluate the prognoses of EGBM and APXApatients. The presence of heterogeneous EZH2 expression in biphasic EGBMs could also contribute to malignant progression.
Authors: Krissie Lenting; Corina N A M van den Heuvel; Anne van Ewijk; Duaa ElMelik; Remco de Boer; Elizabeth Tindall; Ge Wei; Benno Kusters; Maarten Te Dorsthorst; Mark Ter Laan; Martijn A Huynen; William P Leenders Journal: Acta Neuropathol Commun Date: 2019-11-20 Impact factor: 7.801