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

J Neurooncol. 2019 Aug;144(1):137-146. doi: 10.1007/s11060-019-03212-0. Epub 2019 Jun 18.


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.

Keywords: Anaplastic pleomorphic xanthoastrocytoma; BRAF V600E; CDKN2A/B; EZH2; Epithelioid glioblastoma.

MeSH terms

  • Adolescent
  • Adult
  • Astrocytoma / classification
  • Astrocytoma / genetics
  • Astrocytoma / metabolism
  • Astrocytoma / pathology*
  • Biomarkers, Tumor / analysis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Child
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelioid Cells / metabolism
  • Epithelioid Cells / pathology
  • Female
  • Follow-Up Studies
  • Gene Deletion*
  • Humans
  • Male
  • Mutation*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Survival Rate
  • Young Adult


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf