BIOM-11. PROGNOSTIC VALUE OF H3K27ME3 AND EZH2 IN ASTROCYTOMA, IDH-MUTANT

Abstract BACKGROUND H3K27 trimethylation (H3K27me3), catalyzed by EZH2, regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a surrogate marker in pathology for diffuse midline glioma, ependymoma. However, the clinical value of H3K27me3 and EZH2 in astrocytoma, IDH-mutant has not been reported. The aim of this study was to evaluate the clinical significance of H3K27me3 and EZH2 in astrocytoma, IDH-mutant. METHODS A total of 30 patients with astrocytoma, IDH-mutant treated at our institute were included. The patients were divided into 2 groups according to the expression of immunohistochemistry (IHC) for H3K27me3. The following factors were analyzed; age, WHO grade, IHC for EZH2, CDKN2A status, ki67-index and extent of resection. The CDKN2A status was diagnosed by IHC for MTAP and was confirmed by NGS-based CGP test in some cases. Kaplan–Meier analysis and Cox regression analysis were performed to analyze overall survival (OS) and progression-free survival (PFS). RESULTS According to WHO classification 2021, astrocytomas were classified as follows: WHO grade2: 20 cases, grade 3: 2 cases, grade 4: 8 cases. Seventeen patients were identified as H3K27me3 positive, while fourteen patients were classified as H3K27me3 negative. The proportion of WHO grade 3 or 4 and ki-67 index were significantly higher in the H3K27me3 positive group (p=0.0011, 0.0036, respectively). OS and PFS were significantly longer in H3K27me3 positive group (p=0.0379, 0.0025). Furthermore, in the analysis of WHO grade 2/3, double-positive expression of H3K27me3 and EZH2 showed significantly shorter PFS and OS than the other group (p=0.0114 and 0.0068, respectively). In Cox regression analysis, H3K27me3 showed the highest likelihood ratio for OS (p=0.01061). CONCLUSIONS In Astrocytoma, IDH-mutant, the H3K27me3 positive group showed poor prognosis than H3K27me3 negative group. In addition, patients with double-positive expression of H3K27me3 and EZH2 demonstrated more unfavorable prognosis. H3K27me3 and EZH2 could be prognostic markers for astrocytoma, IDH-mutant.