Clinicopathologic and FISH-Based Evaluation of CDKN2A/B and EGFR in IDH Mutant Astrocytomas

Introduction: Isocitrate dehydrogenase(IDH)-mutant astrocytomas represent a biologically distinct but clinically heterogeneous lineage. In the World Health Organization Central Nervous System 5 (WHO, CNS) classification, CDKN2A/B homozygous deletion is a grade 4-defining alteration, while Epidermal growth factor receptor (EGFR) amplification is primarily associated with IDH-wildtype glioblastomas. This study evaluates the frequency and prognostic significance of these alterations in strictly defined IDH-mutant astrocytomas. Methods: We analyzed 39 supratentorial IDH-mutant astrocytomas diagnosed between 2016 and 2020. CDKN2A/B deletion and EGFR amplification were assessed via routine fluorescence in situ hybridization (FISH) based testing and correlated with histologic parameters and clinical outcomes. Results: CDKN2A/B deletion was identified in 61.5% of cases; however, high-level homozygous deletion (≥30% of nuclei) was present in only two cases. Epidermal growth factor receptor amplification was absent in all evaluable tumors. Neither WHO grade nor mitotic activity demonstrated a significant correlation with overall or disease-free survival. Notably, patients with high-level CDKN2A/B homozygous deletion remained alive without high-grade transformation at last follow-up. Conclusion: These findings highlight the limited prognostic value of morphology within this molecular lineage and underscore the necessity of integrating molecular biomarkers into diagnostic frameworks. Larger multicenter cohorts with extended follow-up are essential to clarify the long-term prognostic significance of specific CDKN2A/B alterations.