Study of Histomolecular Classification of Glioma-Integrating Histology and Molecular Analysis in the Diagnosis of Brain Tumors
Received: 07. Dezember 2017
accepted after revision: 16. April 2018
10. August 2018 (online)
Introduction The updated 2016 classification of gliomas incorporates well-established molecular parameters into the classification of diffuse gliomas, taking into account isocitrate dehydrogenase 1 (IDH1) mutation, α-thalassemia/mental retardation syndrome X-linked (ATRX) loss, and 1p/19q co-deletion.
Aim and Objectives To study IDH1 and ATRX mutations in gliomas, 1p/19q co-deletion by fluorescent in situ hybridization (FISH) in oligodendroglioma, and to correlate IDH1, ATRX, and 1p/19q with tumor type and grade.
Material and Methods Total 73 cases of gliomas were diagnosed on histology and graded as astrocytoma (grades 2–4), oligodendroglioma (grades 2–3), and oligoastrocytoma (grades 2–3) by two pathologists independently. IDH mutation and ATRX expression were analyzed using immunohistochemistry in all cases whereas 1p/19q co-deletion was studied using FISH in cases with oligodendroglioma and oligoastrocytoma morphology.
Results Total 48 cases of astrocytoma, 9 cases of oligoastrocytoma, and 16 cases of oligodendroglioma were included. The maximum number of IDH1 mutation cases were seen in diffuse astrocytoma (7/10; 70%) as compared with anaplastic astrocytoma (5/15; 33.33%), glioblastoma multiforme (GBM) (3/23; 13.04%) grade II oligoastrocytoma (3/6; 50%), anaplastic oligoastrocytoma (2/3; 66.67%), and oligodendroglioma grade II (7/10; 70%). ATRX loss was seen in diffuse astrocytoma grade II (6/10; 60%), anaplastic astrocytoma (6/15; 40%), oligoastrocytoma grade II (2/6; 33.33%), and anaplastic oligoastrocytoma (1/3; 33.33%). 1p/19q co-deletion was seen in oligoastrocytoma (2/2; 100%), anaplastic oligoastrocytoma (1/2; 50%), oligodendroglioma (3/4; 75%), and anaplastic oligodendroglioma (1/3; 33.33%). Six of the seven cases with 1p/19q co-deletion also showed IDH1 mutation. One of seven 1p/19q co-deleted cases had loss of expression of ATRX.
Conclusion Incorporation of IDH1 mutation, ATRX loss, and 1p/19q co-deletion molecular studies help in a more accurate diagnosis and classification of gliomas.
- 1 Boots-Sprenger SHE, Sijben A, Rijntjes J. et al. Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution. Mod Pathol 2013; 26 (07) 922-929
- 2 Dasgupta A, Gupta T, Jalali R. Indian data on central nervous tumors: a summary of published work. South Asian J Cancer 2016; 5 (03) 147-153
- 3 Loussouarn D, Le Loupp AG, Frenel JS. et al. Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol 2012; 40 (06) 2058-2062
- 4 Kannan K, Inagaki A, Silber J. et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012; 3 (10) 1194-1203
- 5 Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep 2013; 13 (05) 345
- 6 Zou P, Xu H, Chen P. et al. IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis. PLoS One 2013; 8 (07) e68782
- 7 Nikiforova MN, Hamilton RL. Molecular diagnostics of gliomas. Arch Pathol Lab Med 2011; 135 (05) 558-568
- 8 Abedalthagafi M, Phillips JJ, Kim GE. et al. The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas. Mod Pathol 2013; 26 (11) 1425-1432
- 9 Jiao Y, Killela PJ, Reitman ZJ. et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 2012; 3 (07) 709-722
- 10 Olar A, Aldape KD. Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol 2014; 232 (02) 165-177
- 11 Weller M, Pfister SM, Wick W, Hegi ME, Reifenberger G, Stupp R. Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol 2013; 14 (09) e370-e379
- 12 Weller M. Management of gliomas: relevance of molecular markers for clinical practice. Eur Assoc of Neurooncol Mag 2012; 2 (01) 6-10
- 13 Mellai M, Piazzi A, Caldera V. et al. IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors. J Neurooncol 2011; 105 (02) 345-357
- 14 Wiestler B, Capper D, Holland-Letz T. et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 2013; 126 (03) 443-451
- 15 Dehais C, Laigle-Donadey F, Marie Y. et al. Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer 2006; 107 (08) 1891-1897
- 16 Lassman AB, Iwamoto FM, Cloughesy TF. et al. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors. Neuro-oncol 2011; 13 (06) 649-659
- 17 Jiang H, Ren X, Cui X. et al. 1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas. Neuro-oncol 2013; 15 (06) 775-782
- 18 Watanabe T, Nobusawa S, Kleihues P, Ohgaki H. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 2009; 174 (04) 1149-1153
- 19 Cai J, Zhu P, Zhang C. et al. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget 2016; 7 (13) 16384-16395
- 20 Mur P, Mollejo M, Hernández-Iglesias T. et al. Molecular classification defines 4 prognostically distinct glioma groups irrespective of diagnosis and grade. J Neuropathol Exp Neurol 2015; 74 (03) 241-249
- 21 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. eds. WHO Classification of Tumours of the Central Nervous System. Revised 4th ed.. Lyon, France: IARC; 2016: 16
- 22 Jenkins RB, Blair H, Ballman KV. et al. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 2006; 66 (20) 9852-9861
- 23 Kaloshi G, Benouaich-Amiel A, Diakite F. et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology 2007; 68 (21) 1831-1836
- 24 Yan H, Parsons DW, Jin G. et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360 (08) 765-773 [Internet]
- 25 Sanson M, Marie Y, Paris S. et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009; 27 (25) 4150-4154