Subgroup stratification of adult diffuse gliomas and outcomes: an adaptation of the updated WHO classification in a resource-constrained environment

Abstract

AbstractIntroduction:The updated World Health Organization 2016 classification of central nervous system tumours recommends the addition of molecular parameters to histological diagnosis. In a resource-constrained setting, molecular testing such as gene sequencing and fluorescence in situ hybridisation is not feasible for all the patients. We assessed the utility of immunohistochemistry (IHC) for isocitrate dehydrogenase (IDH1/R132H) gene and alpha thalassemia/mental retardation syndrome X linked gene (ATRX) to stratify adult diffuse gliomas into subgroups and analysed the outcomes.Materials/Methods:Fifty-eight patients with grades III/IV astrocytic gliomas were tested by IHC for IDH1/R132H and ATRX mutation as per the standard protocol and were later stratified into three subgroups based on IHC. IDH1/R132H positive/ATRX retained gliomas were stratified as group 1 (G1), IDH1/R132H positive/ATRX lost were grouped as G2 and IDH1/R132H negative (with or without ATRX loss) as G3. All patients underwent adjuvant therapy as per the Stupp regimen. Outcomes and survival were analysed by Kaplan–Meier analysis using SPSS 21.v.Results:Median age of the cohort of 58 patients (male: 39, female: 19) was 40 years. Histologically, glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) and anaplastic oligodendroglioma (AOD) were seen in 23:17:18 patients. Forty-eight percent were tested positive for IDH1/R132H, 62% had retained ATRX protein stratifying patients into three subgroups (G1:14, G2:14, G3:30). The G3 group contained both AA and GBM cases. At median follow-up of 18 months, overall survival (OS) of the entire cohort was 76%, higher in G1, compared to G2 and G3 (log-rank p = 0·01). In comparison to various factors such as age, gender, location of the lesion and presenting symptom on survival among various groups, we found that gender of the patient in group I (men vs. women, p = 0·02), laterality of the tumour in group II (right vs. left, p = 0·07) and age of the patient in group III (<45 vs. >45, p = 0·01) demonstrated significant impact on OS.Conclusion:Subgroup stratification of adult diffuse gliomas based on IHC for IDH/R132H and ATRX demonstrates that group 1 was the most favourable prognostic factor. In a resource-constrained environment, IHC alone may guide appropriate management decision for the majority of adult diffuse gliomas, gene sequencing reserved for IDH1/R132H negative GBM in patients less than 45 years of age.