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CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization
Manali Ranade1, Sridhar Epari2, Omshree Shetty1
1Department of Pathology (Molecular Pathology Division), Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
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.
Insights
CDKN2A/B homozygous deletion is found in IDH-mutant astrocytic tumors across all grades, more frequently in higher grades. Fluorescence in-situ hybridization (FISH) is a reliable method for its detection.
Area of Science:
- Neuro-oncology
- Cancer genetics
- Molecular pathology
Background:
- CDKN2A/B homozygous deletion is a key feature of IDH-mutant astrocytic tumors, particularly grade 4.
- Understanding its prevalence and impact is crucial for diagnosis and prognosis.
Purpose of the Study:
- To evaluate the CDKN2A/B homozygous deletion in IDH-mutant astrocytic tumors.
- To assess the clinicopathological significance of CDKN2A/B deletion.
Main Methods:
- CDKN2A/B homozygous deletion was assessed using Fluorescence in-situ hybridization (FISH).
- Two recently accepted interpretation methods were employed and compared.
- Inter-observer agreement was evaluated using Kappa statistics.
Main Results:
- CDKN2A/B deletion was detected in IDH-mutant astrocytic tumors across all histological grades (2, 3, and 4).
- Higher detection rates were observed in higher-grade tumors (90% in grade 4 vs. 71% in lower grades).
- FISH demonstrated good agreement between interpretation methods (Kappa = 0.75) and showed an inverse correlation with MIB-1 labeling index.
Conclusions:
- CDKN2A/B homozygous deletion is present in IDH-mutant astrocytic tumors across all grades, with increased frequency in higher grades.
- FISH is a viable and reliable method for detecting CDKN2A/B homozygous deletion in these tumors.
- No significant correlation was found with other clinicopathological parameters or disease progression frequency.
