A single-centre observational study of 124 surgically managed glioma patients: molecular subtyping and its correlation with clinico-radiological profile

Ashutosh Singh, Suyash Singh, Sarita Agrawal, Jyoti Verma, Shalini Singh, Prabhakar Misra, Awadhesh Kumar Jaiswal, Sanjay Behari, Sushila Jaiswal


Background: The World Health Organization (WHO) 2016 classification incorporated molecular subtyping in glioma, highlighting the diagnostic and prognostic significance. The study aims to determine the isocitrate dehydrogenase (IDH-1) gene, α-thalassemia/mental retardation syndrome X-linked (ATRX) gene, and tumor suppressor gene-53 (p53) mutation in glioma and their correlation with various clinical and radiological parameters.

Methods: In this prospective observational study, histopathological slides of glioma (2017-2018), were analyzed for IDH-1, ATRX and p53 mutations and their correlation with various clinical and radiological parameters.

Results: IDH-1 mutation was found in 48 (38.7%), ATRX loss in 38 (30.6%) and p53 mutation in 40 (32.5%) patients. The expression of IDH-1 was significantly higher (43.7%) in adults; however, no significant difference was seen with gender. Also 51.2% of patients, who presented with seizures, showed IDH-1 expression; and 27.7% of patients, who had neurological deficit also showed IDH-1 expression. IDH-1 expression was high in glioma located at insula (73.3%) and parietal lobe (71.4%); while ATRX loss was seen in glioma located at insula (80%). Intraventricular glioma characteristically lacks all three markers: IDH-1 expression, p53 overexpression and ATRX loss. IDH-1 expression and p53 overexpression was seen mainly in diffuse fibrillary astrocytoma, oligodendroglioma, anaplastic astrocytoma and glioblastoma.

Conclusions: Molecular subtyping is of paramount importance in glioma management. IDH-1 mutation is commonly observed in adults and patients presenting with seizures. The duration of symptoms correlates with IDH-1 and ATRX mutations. Hypothalamic tumors lack all three mutations.


Isocitrate dehydrogenase-1 mutation, Glioma, Immunohistochemistry, α-thalassemia/mental retardation syndrome X-linked gene, Tumor suppressor gene-53, Astrocytic tumors

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Davis ME. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5):2-8.

Stoyanov GS, Dzhenkov DL. On the concepts and history of glioblastoma multiforme-morphology, genetics and epigenetics. Folia Med (Plovdiv). 2018;60(1):48-66.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97-109.

Masui K, Onizuka H, Cavenee WK, Mischel PS, Shibata N. Metabolic reprogramming in the pathogenesis of glioma: Update. Neuropathol. 2019;39(1):3-13.

Gladson CL, Prayson RA, Liu WM. The pathobiology of glioma tumors. Annu Rev Pathol. 2010;5:33-50.

Jacobs DI, Fukumura K, Bainbridge MN, Armstrong GN, Tsavachidis S, Gu X, et al. Elucidating the molecular pathogenesis of glioma: integrated germline and somatic profiling of a familial glioma case series. Neuro Oncol. 2018;20(12):1625-33.

Zhang Y, Dube C, Gibert M Jr, Cruickshanks N, Wang B, Coughlan M, et al. The p53 pathway in glioblastoma. Cancers (Basel). 2018;10(9):297.

Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep. 2013;13(5):345.

Wood MD, Halfpenny AM, Moore SR. Applications of molecular neuro-oncology-a review of diffuse glioma integrated diagnosis and emerging molecular entities. Diagn Pathol. 2019;14:29.

Huang J, Yu J, Tu L, Huang N, Li H, Luo Y. isocitrate dehydrogenase mutations in glioma: from basic discovery to therapeutics development. Front Oncol. 2019;12(9):506.

Birner P, Toumangelova-Uzeir K, Natchev S, Guentchev M. Expression of mutated isocitrate dehydrogenase-1 in gliomas is associated with p53 and EGFR expression. Folia Neuropathol. 2011;49(2):88-93.

Chaurasia A, Park SH, Seo JW, Park CK. Immunohistochemical analysis of ATRX, IDH1 and p53 in glioblastoma and their correlations with patient survival. J Korean Med Sci. 2016;31(8):1208-14.

Jaiswal S, Chaudhary N, Prasad P, Khatri D, Das KK, Mehrotra A, et al. Expression of isocitrate dehydrogenase-1 (IDH-1) mutant protein in gliomas. Tech Neurosurg Neurol. 2018;1(3).

Haase S, Garcia-Fabiani MB, Carney S, Altshuler D, Núñez FJ, Méndez FM, et al. Mutant ATRX: uncovering a new therapeutic target for glioma. Expert Opin Ther Targets. 2018;22(7):599-613.

Nandakumar P, Mansouri A, Das S. The role of ATRX in glioma biology. Front Oncol. 2017;7:236.

England B, Huang T, Karsy M. Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme. Tumour Biol. 2013;34(4):2063-74.

Jin Y, Xiao W, Song T, Feng G, Dai Z. Erratum to: expression and prognostic significance of p53 in glioma patients: a meta-analysis. Neurochem Res. 2016;41(12):3418.

Dong C, Yuan Z, Li Q, Wang Y. The clinicopathological and prognostic significance of TP53 alteration in K27M mutated gliomas: an individual-participant data meta-analysis. Neurol Sci. 2018;39(7):1191-201.

Han J, Puri RK. Analysis of the cancer genome atlas (TCGA) database identifies an inverse relationship between interleukin-13 receptor α1 and α2 gene expression and poor prognosis and drug resistance in subjects with glioblastoma multiforme. J Neurooncol. 2018;136(3):463-74.

Karnam S, Kottu R, Chowhan AK, Bodepati PC. Expression of p53 & epidermal growth factor receptor in glioblastoma. Indian J Med Res. 2017;146:738-45.

Shiraishi S, Tada K, Nakamura H, Makino K, Kochi M, Saya H, Kuratsu J, Ushio Y. Influence of p53 mutations on prognosis of patients with glioblastoma. Cancer. 2002;95(2):249-57.

Pollack IF. IDH-1 mutations are common in malignant gliomas arising in adolescents: A report from children’s oncology group. Childs Nerv Syst. 2011;27:87-94.

Bleeker FE. IDH-1 mutations at residue p.R132 (IDH-1R132) occur frequently in high grade glioma but not in other solid tumors. Hum Mutat. 2009;30:7-11.

Stockhammer F. IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom. Seizure. 2012;21:194-7.

Rasheed BK, McLendon RE, Herndon JE, Friedman HS, Friedman AH, Bigner DD, et al. Alterations of the TP53 gene in human gliomas. Cancer Res. 1994;54(5):1324-30.

Cunningham JM, Kimmel DW, Scheithauer BW, O'Fallon JR, Novotny PJ, Jenkins RB. Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value. J Neurosurg. 1997;86(1):121-30.

Ikemura M, Shibahara J, Mukasa A, Takayanagi S, Aihara K, Saito N, et al. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathol. 2016;69(2):260-7.

Carrillo JA. Relationship between tumor enhancement, edema, IDH-1 mutational status, MGMT promotor methylation and survival in glioblastoma. Am J Neurorad. 2012;33:1349-55.

Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang D-A, Fontebasso AM, et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol. 2012;124:615-25.

Sarkar C, Karak AK, Nath N, Sharma MC, Mahapatra AK, Chattopadhyay P, et al. Apoptosis and proliferation: correlation with p53 in astrocytic tumours. J Neurooncol. 2005;73(2):93-100.

Mistry AM, Wooten DJ, Davis LT, Mobley BC, Quaranta V, Ihrie RA. Ventricular-subventricular zone contact by glioblastoma is not associated with molecular signatures in bulk tumor data. Sci Rep. 2019;9(1):1842.

Eseonu CI, ReFaey K, Garcia O, Raghuraman G, Quinones-Hinojosa A. Volumetric analysis of extent of resection, survival, and surgical outcomes for insular gliomas. World Neurosurg. 2017;103:265-74.

Beverly I De Leeuw, Kirsten M Van Baarsen, Tom J Snijders, Pierre A J T Robe. Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis. Neuro-Oncol Adv. 2019;1(1):32.

Tang C, Zhang ZY, Chen LC, Sun Z, Zhang Y, Qin Z, et al. Subgroup characteristics of insular low-grade glioma based on clinical and molecular analysis of 42 cases. J Neurooncol. 2016;126(3):499-507.