Vega Karlowee1,2, Vishwa Jeet Amatya3, Takeshi Takayasu4, Motoki Takano4, Ushio Yonezawa4, Yukio Takeshima3, Kazuhiko Sugiyama5, Kaoru Kurisu4, Fumiyuki Yamasaki4. 1. Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, ve94karlowee@gmail.com. 2. Department of Anatomical Pathology, Diponegoro University, Semarang, Indonesia, ve94karlowee@gmail.com. 3. Department of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 4. Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 5. Department of Clinical Oncology & Neuro-Oncology Program, Hiroshima University, Hiroshima, Japan.
Abstract
INTRODUCTION: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival. METHODS: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies. RESULTS: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV. CONCLUSION: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved.
INTRODUCTION: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival. METHODS: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies. RESULTS: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV. CONCLUSION: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved.
Authors: Huy Gia Vuong; Hieu Trong Le; Tam N M Ngo; Kar-Ming Fung; James D Battiste; Rene McNall-Knapp; Ian F Dunn Journal: J Neurooncol Date: 2021-11-18 Impact factor: 4.130
Authors: Huy Gia Vuong; Tam N M Ngo; Hieu Trong Le; Andrew Jea; Maya Hrachova; James Battiste; Rene McNall-Knapp; Ian F Dunn Journal: Front Oncol Date: 2022-03-18 Impact factor: 6.244