{"title":"Prognostic value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant.","authors":"Shumpei Onishi, Fumiyuki Yamasaki, Vishwa Jeet Amatya, Ushio Yonezawa, Akira Taguchi, Iori Ozono, Novita Ikbar Khairunnisa, Yukari Go, Yukio Takeshima, Nobutaka Horie","doi":"10.1007/s11060-024-04897-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>H3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2-H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation.</p><p><strong>Methods: </strong>Thirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan-Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results.</p><p><strong>Results: </strong>The mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively).</p><p><strong>Conclusion: </strong>Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuro-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11060-024-04897-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: H3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2-H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation.
Methods: Thirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan-Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results.
Results: The mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively).
Conclusion: Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.
期刊介绍：
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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