IDH1 , ATRX , and BRAF V600E mutation in astrocytic tumors and their significance in patient outcome in north Indian population.

Background: According to the current World Health Organization (WHO) classification of central nervous system (CNS) tumors (2016), histological diagnosis of gliomas should be supplemented by molecular information. This study was carried out to determine the frequency of isocitrate dehydrogenase 1 ( IDH 1), ATRX , and BRAF V600E mutations in different grade astrocytomas and their prognostic value.

Methods: Eighty cases of astrocytoma (15 pilocytic astrocytoma, 25 diffuse astrocytoma, 15 anaplastic astrocytoma, and 25 glioblastoma) with follow-up information were analyzed using immunohistochemistry for IDH1 mutant protein, ATRX, p53, and BRAF. Sanger sequencing was carried out for IDH1 exon 4 and BRAF exon 15.

Results: All pilocytic astrocytoma and primary glioblastoma cases were negative for IDH1 mutation. IDH1 mutation was detected in 80% (20/25) DA and 87% (13/15) AA cases. IDH1 R132H was the commonest IDH1 mutation (94.1%) and immunohistochemistry showed 100% sensitivity and specificity to detect this mutation. Loss of nuclear ATRX expression was found in 87% (20/23) and 100% (14/14) DA and AA cases, respectively. IDH1 mutant DA patients had longer overall survival than IDH1 wild cases, although this difference was not significant (79.5 months vs. 42.5 months, P value 0.417). BRAF V600E mutation was not detected in any astrocytic tumor.

Conclusions: IDH1 and ATRX mutations are very common in diffuse astrocytoma and anaplastic astrocytoma, while they are rare in pilocytic astrocytoma and glioblastoma. Immunohistochemistry for IDH1 and ATRX can successfully characterize the diffuse gliomas into molecularly defined groups in majority of the cases. BRAF V600E mutation is rare in astrocytic tumors in Indian population.