PATH-33. THE IMPACT OF THE MOLECULAR CLASSIFICATION IN HISTOLOGICALLY DIAGNOSED GLIOBLASTOMAS

Abstract OBJECTIVE Glioblastomas have been diagnosed based on traditional histological findings (necrosis, microvascular proliferation) and molecular genetic findings (IDH-wildtype, H3-wildtype, TERT promoter mutation, EGFR amplification, +7/−10 chromosome copy-number changes). Thus, IDH-wildtype and H3-wildtype glioblastomas can be classified into those with molecular genetic findings (defined as molecular glioblastoma) and those with only histological findings (defined as non-molecular glioblastoma). We re-evaluated the molecular genetics of patients diagnosed histologically with glioblastoma at our institution and examined their characteristics. METHODS A total of 275 cases diagnosed histologically as glioblastoma between December 2000 and March 2022 were included. Sanger sequencing (IDH1/2, Histone H3, TERTp) and MLPA for copy number analysis (PDGFRA, EGFR, CDKN2A, PTEN, MDM2, CDK4, TP53) were performed. The genetic analysis results and survival periods were analyzed. RESULTS Among the 275 cases, 151 initial glioblastomas met the criteria of IDH wild-type and H3 wild-type. Genetic analysis results that could be evaluated were obtained in 89 of these cases. TERT promoter mutation was present in 43 cases (48%), with 37% (16 cases) showing EGFR amplification and 19% (8 cases) showing EGFR gain/PTEN loss (+7/-10) simultaneously. On the other hand, TERT promoter wild-type was found in 45 cases (51%), with EGFR amplification in only 1 case (2%) and EGFR ain/PTEN loss in 4 cases (9%), and these 5 cases were judged to correspond to molecular glioblastoma. Adding one case with TERT promoter evaluation failure but EGFR amplification, the integrated molecular/non-molecular glioblastoma cases were 49 (55%)/40 (45%), revealing that both tumor types exist in nearly equal proportions. Survival curve analysis showed that median overall survivals of molecular and non-molecular glioblastoma were 17 and 29 months, respectively, showing a two-fold difference, and non-molecular glioblastoma had significantly better prognosis (P=0.0136). CONCLUSION It was revealed that tumors diagnosed as glioblastoma based on conventional histological findings can be broadly classified into molecular and non-molecular glioblastoma, with significant differences in prognosis.