Path-22. clinical and molecular neuropathological features of epithelioid glioblastoma

Abstract BACKGROUND Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM. METHODS Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. RESULTS E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. CONCLUSION The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.