Clinicopathological correlation of glioma patients with respect to immunohistochemistry markers: A prospective study of 115 patients in a Tertiary Care Hospital in North India

Gitanshu Dahuja; Ashok Gupta; Arpita Jindal; Gaurav Jain; Santosh Sharma; Arvind Kumar

doi:10.4103/ajns.AJNS_377_20

Asian Journal of Neurosurgery, Table of Contents

CC BY-NC-ND 4.0 · Asian J Neurosurg 2021; 16(04): 732-737
DOI: 10.4103/ajns.AJNS_377_20

Original Article

Clinicopathological correlation of glioma patients with respect to immunohistochemistry markers: A prospective study of 115 patients in a Tertiary Care Hospital in North India

Authors

Gitanshu Dahuja

Department of Neurosurgery, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan
Ashok Gupta

Department of Neurosurgery, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan
Arpita Jindal

¹Department of Pathology, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan
Gaurav Jain

Department of Neurosurgery, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan
Santosh Sharma

¹Department of Pathology, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan
Arvind Kumar

Department of Neurosurgery, Swai Maan Singh Medical College and Attached Hospital, Jaipur, Rajasthan

Abstract

Background: With the incorporation of molecular subtyping in glioma patients in 2016 WHO classification, there is a need to understand the immunohistochemistry (IHC) marker expression in various glioma patients and to clinically correlate with various subgroups. Objective: Aim of the study was to assess IHC marker expression profile in glioma patients and to clinically correlate them in various subgroups. Materials and Methods: The prospective study included 115 glioma patients. IHC markers (isocitrate dehydrogenase [IDH] 1, ATRX, P53, Ki-67 antibody) were done in all patients. Patients received treatment as per the grade of tumor. The patients were followed in 3 monthly intervals, for a period of 12 months. SPSS software version 20.0 was used for statistical analysis. Tables were prepared in Microsoft Excel sheet. Kaplan–Meier method was used for survival analysis. Results: There were 11 Grade 1, 33 Grade 2, 26 Grade 3, and 45 glioblastoma multiforme (GBM) patients out of which 10 patients were secondary GBM cases. IDH1 mutation is frequent in Grade 2 and Grade 3 tumors of both astrocytic and oligodendroglia tumors. Its mutation is also common in secondary GBM patients. ATRX mutation is specific to astrocytic lineage, Grade 2, Grade 3, and secondary GBM patients. Conclusion: Molecular nature of DA and AA cases can be accurately confirmed by combined IDH1 and ATRX IHC thereby avoiding costly investigations such as fluorescence in situ hybridization. In astrocytic tumors, p53 can act as a surrogate marker. IDH-mutant glioma patients have better prognoses than IDH wild gliomas.

Key-words:

ATRX - GLIOMA - immunohistochemistry - isocitrate dehydrogenase 1

Full Text

References

References
1 Goyal R, Mathur SK, Gupta S, Goyal R, Kumar S, Batra A, et al. Immunohistochemical expression of glial fibrillary acidic protein and CAM5.2 in glial tumors and their role in differentiating glial tumors from metastatic tumors of central nervous system. J Neurosci Rural Pract 2015;6:499-503.
2 Madabhushi V, Venkata RI, Garikaparthi S, Kakarala SV, Duttaluru SS. Role of immunohistochemistry in diagnosis of brain tumors: A single institutional experience. J NTR Univ Health Sci 2015;4:103-11.
3 Mukherjee T, Dutta R, Ghosh J, Sharma M. Brain tumors with review of literature: Immunohistochemistry or biomarkers versus histomorphology. Neurooncol Open Access 2016;1.
4 Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol 2016;131:803-20.
5 Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B, et al. Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas. Neuro Oncol 2016;18:1099-108.
6 Fan Z, Liu Y, Li S, Liu X, Jiang T, Wang Y, et al. Association of tumor growth rates with molecular biomarker status: A longitudinal study of high-grade glioma. Aging (Albany NY) 2020;12:7908-26.
7 Cai J, Zhang C, Zhang W, Wang G, Yao K, Wang Z, et al. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors. Oncoscience 2016;3:258-65.
8 Rodriguez FJ, Vizcaino MA, Lin MT. Recent advances on the molecular pathology of glial neoplasms in children and adults. J Mol Diagn 2016;18:620-34.
9 Takano S, Ishikawa E, Sakamoto N, Matsuda M, Akutsu H, Noguchi M, et al. Immunohistochemistry on IDH ½, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas. Brain Tumor Pathol 2016;33:107-16.
10 Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481-98.
11 Jaiswal S. Role of immunohistochemistry in the diagnosis of central nervous system tumors. Neurol India 2016;64:502-12.
12 Chatterjee D, Radotra BD, Kumar N, Vasishta RK, Gupta SK. IDH1, ATRX, and BRAFV600E mutation in astrocytic tumors and their significance in patient outcome in north Indian population. Surg Neurol Int 2018;9:29.
13 Ichimura K, Pearson DM, Kocialkowski S, Bäcklund LM, Chan R, Jones DT, et al. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol 2009;11:341-7.
14 Zou P, Xu H, Chen P, Yan Q, Zhao L, Zhao P, et al. IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: A meta-analysis. PLoS One 2013;8:e68782.
15 Agarwal S, Sharma MC, Jha P, Pathak P, Suri V, Sarkar C, et al. Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing. Neuro Oncol 2013;15:718-26.
16 Zeng A, Hu Q, Liu Y, Wang Z, Cui X, Li R, et al. IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma. Oncotarget 2015;6:30232-8.
17 Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: A prospective translational study of the German Glioma Network. J Clin Oncol 2009;27:5743-50.
18 Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009;27:4150-4.
19 Thon N, Eigenbrod S, Kreth S, Lutz J, Tonn JC, Kretzschmar H, et al. IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival. Cancer 2012;118:452-60.
20 Reuss DE, Mamatjan Y, Schrimpf D, Capper D, Hovestadt V, Kratz A, et al. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: A grading problem for WHO. Acta Neuropathol 2015;129:867-73.
21 Park SH, Won J, Kim SI, Lee Y, Park CK, Kim SK, et al. Molecular testing of brain tumor. J Pathol Transl Med 2017;51:205-23.
22 Khan I, Waqas M, Shamim MS. Prognostic significance of IDH 1 mutation in patients with glioblastoma multiforme. J Pak Med Assoc 2017;67:816-7.
23 Pai T, Epari S, Desai S, Wadile A, Gupta T, Goda JS, et al. Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion. Neurol India 2017;65:113-20.
24 Shao LW, Pan Y, Qi XL, Li YX, Ma XL, Yi WN, et al. ATRX loss in adult supratentorial diffuse astrocytomas correlates with p53 over expression and IDH1 mutation and predicts better outcome in p53 accumulated patients. Histol Histopathol 2016;31:103-14.
25 Thon N, Eigenbrod S, Grasbon-Frodl EM, Ruiter M, Mehrkens JH, Kreth S, et al. Novel molecular sterotactic biopsy procedures reveal intratumoral homogeneity of loss of hetrozygosity of 1p/19q and TP53 mutation in World Health Organisation grade 2 gliomas. J Neuropathol Exp Neurol 2009;68:1219-28.
26 Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J, Kastenhuber ER, et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012;3:1194-203.
27 Skjulsvik AJ, Mørk JN, Torp MO, Torp SH. Ki-67/MIB-1 immunostaining in a cohort of human gliomas. Int J Clin Exp Pathol 2014;7:8905-10.