Analysis of Isocitrate Dehydrogenase (IDH) expression in astrocytoma patients: cases of South Sulawesi, Indonesia

Olivia Desty Sabunga; Cahyono Kaelan; Upik Anderiani Miskad; Andi Alfian Zainuddin; Ni Ketut Sungowati; Muhammad Husni Cangara

doi:10.15562/bmj.v11i1.3078

Analysis of Isocitrate Dehydrogenase (IDH) expression in astrocytoma patients: cases of South Sulawesi, Indonesia

Olivia Desty Sabunga ,

Cahyono Kaelan ,

Upik Anderiani Miskad ,

Andi Alfian Zainuddin ,

Ni Ketut Sungowati ,

Muhammad Husni Cangara ,

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DOI: https://doi.org/10.15562/bmj.v11i1.3078 |
Published: 2022-04-08

Abstract

Background: Astrocytoma is the most common primary intracerebral tumor in adults and causes high morbidity and mortality. Most patients with astrocytomas, especially diffuse gliomas, have a poor prognosis. Recent genetic and epigenetic studies have shown that mutations in the Isocitrate Dehydrogenase (IDH) gene play an important role in the pathogenesis and prognosis of gliomas, thus facilitating IDH1 mutations in the population to become an important marker, not only to assist in the diagnosis and prognostic factors of these gliomas but also to develop therapeutic targets as currently available. This study aims to see differences in the expression of the IDH in each astrocytoma classification.

Methods: A cross-sectional analytic study was conducted at the Anatomical Pathology Laboratory, Faculty of Medicine, Universitas Hasanuddin, from October 2020 to August 2021. The research sample came from 65 paraffin block preparations for primary brain tumors with the diagnosis of Diffuse Astrocytoma (DA), Anaplastic Astrocytoma (AA) and Glioblastoma (GB). The immunohistochemical staining was performed using the monoclonal antibody IDH1-R132H. The microscopic assessment was carried out using a light microscope. Data were analyzed using SPSS version 20 for Windows.

Results: There was a significant relationship between the expression of IDH1-R132H in each astrocytoma classification (p=0.008). The prevalence of astrocytoma with negative IDH1-R132H expression (IDH-wildtype) is lower by 21 samples (32.3%) compared to astrocytoma with positive IDH1-R132H expression (IDH-mutant), which is 44 samples (67.7%).

Conclusion: There are significant differences in the expression of IDH1-R132H in Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma, where the proportion of IDH-mutant status is higher than IDH-wildtype and IDH1 mutation status has a significant relationship with tumor grade.

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Bell JS, Koffie RM, Rattani A, Dewan MC, Baticulon RE, Qureshi MM, et al. Global incidence of brain and spinal tumors by geographic region and income level based on cancer registry data. J Clin Neurosci. 2019;66:121-127.
Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro Oncol. 2017;19(11):1553-1564.
Rasmussen BK, Hansen S, Laursen RJ, Kosteljanetz M, Schultz H, Nørgård BM, et al. Epidemiology of glioma: clinical characteristics, symptoms, and predictors of glioma patients grade I-IV in the the Danish Neuro-Oncology Registry. J Neurooncol. 2017;135(3):571-579.
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
DeWitt JC, Mock A, Louis DN. The 2016 WHO classification of central nervous system tumors: what neurologists need to know. Curr Opin Neurol. 2017;30(6):643-649.
Malueka RG, Theresia E, Fitria F, Argo IW, Donurizki AD, Shaleh S, et al. Comparison of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, Immunohistochemistry, and DNA Sequencing for the Detection of IDH1 Mutations in Gliomas. Asian Pac J Cancer Prev. 2020;21(11):3229-3234.
Gargini R, Segura-Collar B, Sánchez-Gómez P. Cellular Plasticity and Tumor Microenvironment in Gliomas: The Struggle to Hit a Moving Target. Cancers (Basel). 2020;12(6):1622.
Metellus P, Colin C, Taieb D, Guedj E, Nanni-Metellus I, de Paula AM, et al. IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J Neurooncol. 2011;105(3):591-600.
Omer NS, Jalal JA, Ismael AT. IDH1(R132H) Immunoexpression in Glioma. Journal of Kurdistan Board of Medical Specialties. 2018;4(1):57-63.
Ichimura K. Molecular pathogenesis of IDH mutations in gliomas. Brain Tumor Pathol. 2012;29(3):131-139.
Loussouarn D, Le Loupp AG, Frenel JS, Leclair F, Von Deimling A, Aumont M, et al. Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol. 2012;40(6):2058-62.
Sriwidyani NP, Wahyuniari IAI, Saputra H, Arijana IGKN. IDH1 mutation in Balinese glioma patients and its relationship with clinicopathological parameters. Bali Medical Journal. 2020;9(3):819-822.
Yao Q, Cai G, Yu Q, Shen J, Gu Z, Chen J, et al. IDH1 mutation diminishes aggressive phenotype in glioma stem cells. Int J Oncol. 2018;52(1):270-278.
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;9:506.
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-12.

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

[2] Bell JS, Koffie RM, Rattani A, Dewan MC, Baticulon RE, Qureshi MM, et al. Global incidence of brain and spinal tumors by geographic region and income level based on cancer registry data. J Clin Neurosci. 2019;66:121-127.

[3] Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro Oncol. 2017;19(11):1553-1564.

[4] Rasmussen BK, Hansen S, Laursen RJ, Kosteljanetz M, Schultz H, Nørgård BM, et al. Epidemiology of glioma: clinical characteristics, symptoms, and predictors of glioma patients grade I-IV in the the Danish Neuro-Oncology Registry. J Neurooncol. 2017;135(3):571-579.

[5] Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.

[6] DeWitt JC, Mock A, Louis DN. The 2016 WHO classification of central nervous system tumors: what neurologists need to know. Curr Opin Neurol. 2017;30(6):643-649.

[7] Malueka RG, Theresia E, Fitria F, Argo IW, Donurizki AD, Shaleh S, et al. Comparison of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, Immunohistochemistry, and DNA Sequencing for the Detection of IDH1 Mutations in Gliomas. Asian Pac J Cancer Prev. 2020;21(11):3229-3234.

[8] Gargini R, Segura-Collar B, Sánchez-Gómez P. Cellular Plasticity and Tumor Microenvironment in Gliomas: The Struggle to Hit a Moving Target. Cancers (Basel). 2020;12(6):1622.

[9] Metellus P, Colin C, Taieb D, Guedj E, Nanni-Metellus I, de Paula AM, et al. IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J Neurooncol. 2011;105(3):591-600.

[10] Omer NS, Jalal JA, Ismael AT. IDH1(R132H) Immunoexpression in Glioma. Journal of Kurdistan Board of Medical Specialties. 2018;4(1):57-63.

[11] Ichimura K. Molecular pathogenesis of IDH mutations in gliomas. Brain Tumor Pathol. 2012;29(3):131-139.

[12] Loussouarn D, Le Loupp AG, Frenel JS, Leclair F, Von Deimling A, Aumont M, et al. Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol. 2012;40(6):2058-62.

[13] Sriwidyani NP, Wahyuniari IAI, Saputra H, Arijana IGKN. IDH1 mutation in Balinese glioma patients and its relationship with clinicopathological parameters. Bali Medical Journal. 2020;9(3):819-822.

[14] Yao Q, Cai G, Yu Q, Shen J, Gu Z, Chen J, et al. IDH1 mutation diminishes aggressive phenotype in glioma stem cells. Int J Oncol. 2018;52(1):270-278.

[15] 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;9:506.

[16] Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-12.

Analysis of Isocitrate Dehydrogenase (IDH) expression in astrocytoma patients: cases of South Sulawesi, Indonesia

Abstract

References

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