Study of Surrogate Immunohistochemical Markers IDH1, ATRX, BRAF V600E, and p53 Mutation in Astrocytic and Oligodendroglial Tumors

Abstract Introduction  In consonance with current the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (2016), histological diagnosis of gliomas should be reinforced by molecular information. This study was performed to determine the frequency of isocitrate dehydrogenase 1 (IDH1), α thalassemia/intellectual disability syndrome X-linked (ATRX), p53, and BRAF V600E mutations in different grade astrocytomas and oligodendrogliomas. Methods  Seventy-seven cases of astrocytoma and oligodendroglioma (7 pilocytic astrocytomas, 15 diffuse astrocytomas [DA], 4 anaplastic astrocytomas [AA], 29 glioblastomas [GBM], and 22 oligodendrogliomas) were analyzed using immunohistochemistry for IDH1 mutant protein, ATRX, p53, and BRAF as well as their clinicopathological features assessed. Results  All pilocytic astrocytoma and primary glioblastoma cases were negative for an IDH1 mutation. IDH1 mutation was detected in 66.7% (10/15) of DA, 50% (2/4) of AA, 20.7% (6/29) of glioblastomas, and 81.8% (18/22) of oligodendroglioma cases. Loss of nuclear ATRX expression was found in 86.7% (13/15), 75% (3/4), and 34.5% (10/29) of DA, AA, and GBM cases, respectively. All oligodendroglioma cases showed retained ATRX expression. Both markers were found statistically significant in the above tumors ( p <0.05). BRAF V600E mutation was detected in a single case of pilocytic astrocytoma and pleomorphic xanthoastrocytoma as well as both cases of epithelioid glioblastoma. 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 the majority of the cases. BRAF V600E mutation is rare in astrocytic tumors in the Indian population.