CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence In-Situ Hybridization

Abstract

Abstract Introduction: CDKN2A/B homozygous-deletion is one of the defining features of grade 4 in IDH-mutant astrocytic tumours. Aim: To evaluate CDKN2A/B-deletion in IDH-mutant astrocytic tumours and its clinico-pathological impact. Materials and methods: CDKN2A/B-deletion was evaluated by Fluorescence in-situ hybridisation (FISH) and interpreted by Ambros et al. (method 1) and Marker et al. (method 2) methods. Results: Eighty-three out of 94 cases (histologically - grade 2: 3, grade 3: 46, grade 4: 34) were interpretable on FISH. Concordant CDKN2A/B-deletion was observed in 71% (27/38) of lower-grade tumours (n = 49) and 90% (27/30) of histological grade 4 tumours. Both the interpretation methods showed good agreement (Kappa = 0.75). CDKN2A/B-deletion showed inverse correlation for < 10% MIB-1 labeling index (p = 0.01) while by method-2 showed significant correlation for grade 4 (p = 0.02). No significant correlation was observed for any other clinico-pathological parameters. Twenty-four patients showed progression/recurrence (including deaths), no significant difference in frequency of CDKN2A/B deletion was observed among cases with disease progression across different histological grades. Conclusions: CDKN2A/B-deletion was observed across all the histological grades of IDH-mutant astrocytic tumours, expectedly more in higher grade. FISH, as a method can be used for detection of CDKN2A/B homozygous-deletion, when there is concordant interpretation.