CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization

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 clinicopathological impact.

Materials and methods: CDKN2A/B-deletion was evaluated by Fluorescence in-situ hybridisation (FISH) and interpreted by two recently accepted 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 (n = 34). Both the interpretation methods showed good agreement (Kappa = 0.75). CDKN2A/B-deletion showed an inverse correlation for < 10% MIB-1 labeling index (p = 0.01) while that by method-2 showed a significant correlation for grade 4 (p = 0.02). No significant correlation was observed for any other clinicopathological parameters. Twenty-four patients showed progression/recurrence (including deaths), and 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 the higher grade. FISH, as a method, can be used for the detection of CDKN2A/B homozygous deletion, when there is concordant interpretation.