Prognostic Effect of CDKN2A Homozygous Deletion and Beclin 1 in Isocitrate Dehydrogenase Mutant Glial Tumors

Abstract

Background: In the updated World Health Organization Classification of Central Nervous System Tumors, the presence of CDKN2A/2B homozygous deletion is now recognized as the indicative of Grade 4 in isocitrate dehydrogenase (IDH) mutant astrocytomas, and it is associated with a poor prognosis in Grade 4 astrocytomas. Conversely, Beclin 1, a crucial protein in autophagy initiation, exhibits a bidirectional effect on tumor progression and suppression. The objective of this study is to evaluate CDKN2A homozygous deletion in IDH mutant astrocytomas of varying grades, to compare it with microvascular proliferation (MVP) and palisading necrosis, and to analyze the relationship between these findings and Beclin 1 expression, subsequently comparing them with prognosis. Subjects and Methods: CDKN2A homozygous deletion and Beclin 1 expression were analyzed in 32 cases with IDH-mutant diffuse astrocytomas of Grades 2, 3, and 4. Results: CDKN2A homozygous deletion was detected in one of 10 patients with Grade 2 and in 8 of 17 patients with Grade 4. Beclin 1 was positively stained in 2 of Grade 2 astrocytomas, 4 of Grade 3 astrocytomas, and 9 of Grade 4 astrocytomas. While Beclin 1 expression was present in 5 of 9 cases with CDKN2A homozygous deletion, no expression was observed in four cases. Conclusion: In this study, the prognostic significance of CDKN2A homozygous deletion alone was found to be lower compared to the deletion in combination with MVP and/or necrosis. At the same time, Beclin 1 expression was determined to exert no prognostic significance alone, while it was found to exert a poor prognostic effect in combination with CDKN2A homozygous deletion.

Keywords

• astrocytoma
• autophagy
• beclin 1
• cdkn2a
• fluorescence in situ hybridization
• isocitrate dehydrogenase mutant