PATH-19. DIAGNOSTIC UTILITY OF MOLECULAR PROFILING IN ADULT DIFFUSE GLIOMA

Abstract INTRODUCTION With the publication of World Health Organization Classification of the Central Nervous System Tumors (WHO CNS5), molecular profiling has become essential for the diagnosis of CNS tumors. To test for the diagnostic molecular alterations, we developed a targeted DNA sequencing panel (Nakashima et al. 2024) to analyze 113 genes, chromosomal abnormalities, and MGMT promoter methylation. This study aimed to evaluate our diagnostic approach using the targeted sequencing panel. PATIENTS AND METHODS We included 72 cases of diffuse adult gliomas diagnosed at our institute between June 2023 and May 2024. We analyzed the tumor diagnoses based on the pathological and immunohistochemical findings as well as the targeted sequencing panel findings. RESULTS The tumor diagnoses were as follows: glioblastoma, IDH-wildtype: 32 cases, astrocytoma, IDH-mutant: 17 cases, oligodendroglioma, IDH-mutant and 1p/19q-codeleted: 15 cases, others: 8 cases. Among 32 cases of IDH1/2 mutations, 28 cases (87.5%) with IDH1 R132H mutation were diagnosed by immunohistochemistry using anti-IDH1 R132H antibody, whereas 4 (12.5%) (3 with IDH2 mutation, and 1 with IDH1 R132S) were diagnosed by the targeted sequencing panel. Of the 32 glioblastoma cases, 6 (18.8%) did not show necrosis or microvascular proliferation and were diagnosed based on either TERT promoter mutation, EGFR amplification, or chromosome 7/chromosome 10 abnormalities. Moreover, 24 out of 26 resected cases (92.3%) were diagnosed morphologically, whereas 4 of 6 biopsy cases (66.7%) were diagnosed molecularly (p=0.0056). Among the 17 cases of astrocytoma, IDH-mutant, 2 (11.8%) showed homozygous deletion of CDKN2A/B. There were 4 cases (5.6%) out of 72 that did not satisfy the diagnostic criteria for glioblastoma, astrocytoma, oligodendroglioma. CONCLUSION Approximately 95% of cases were diagnosed based on WHO CNS5 criteria with molecular profiling. We also demonstrate molecular profiling is useful in glioblastoma diagnostics, especially in biopsy cases where morphological diagnostic evidence is not recognized.