Status and prognostic impact of IDH1 in adult grade 4 diffuse gliomas

Authors

  • Mouna Zghal Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia
  • Slim Charfi Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia
  • Wicem Siala Medical Radiotherapy Department, Habib Bourguiba University Hospital Sfax, Tunisia
  • Soumaya Graja Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia
  • Fatma Kolsi Neurosurgery Department, Habib Bourguiba University Hospital Sfax, Tunisia
  • Wafa Ghribi Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia
  • Lobna Ayedi Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia
  • Mohamed Zaher Boudawara Neurosurgery Department, Habib Bourguiba University Hospital Sfax, Tunisia
  • Jamel Daoud Medical Radiotherapy Department, Habib Bourguiba University Hospital Sfax, Tunisia
  • Tahya Sellami Boudawara Pathology Department and Research Laboratory LR18SP10, Habib Bourguiba University Hospital, Sfax, Tunisia

DOI:

https://doi.org/10.25305/unj.333185

Keywords:

grade 4 diffuse glioma, IDH1, astrocytoma grade 4, glioblastoma, pathology, prognosis

Abstract

Background and objectives: The fifth edition of the WHO Classification of Tumors of the Central Nervous System divides grade 4 diffuse glioma based on IDH1 mutation in grade 4 astrocytoma, IDH-mutant and glioblastoma, IDH-wild type tumors. This study aimed to evaluate the IDH1 status in grade 4 diffuse glioma as well as its correlation with clinicopathological features and patient survival. To our knowledge, no Tunisian studies on the molecular profile of diffuse glioma have yet been published.

Methods: This is a retrospective study including all cases of adult, grade 4 diffuse glioma collected in the pathology department of Habib Bourguiba hospital.

Results: A total of 67 patients were included in the final analysis. The expression of IDH1 was positive in 22 cases (32%). IDH1-positive tumors were classified as grade 4 astrocytoma, IDH1-mutant while, 45 IDH1-negative tumors were classified as glioblastoma, IDH1-wild type tumors (68%). IDH1 expression was correlated with younger age (≤ 40 years old), frontal location, complete surgical resection and well-defined borders. IDH1-positive tumors were associated significantly with better prognosis. The 1-year overall survival (OS) for grade 4 astrocytoma, IDH1-mutant was 86% compared with 8% in glioblastoma, IDH1-wild type (p=0.008).

Conclusion: Our study investigated IDH1 expression in grade 4 diffuse glioma and proved that grade 4 astrocytoma, IDH1 positive tumors displayed different characteristics with a more favorable outcome compared to glioblastoma, IDH1 negative. Thus, evaluation of IDH1 mutation should be standardized routinely not only as diagnostic marker but also to refine the prognostic classification of these tumors.

References

1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds): WHO Classification of Tumors of the Central Nervous System (4th edition). IARC; Lyon. 2016.

2. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. (Eds): WHO Classification of Tumors of the central Nervous System (5th edition). IARC; Lyon. 2021.

3. Rousseau A. [Molecular diagnostics of diffuse gliomas]. Revue Francophone des Laboratoires. 2018;(506):61‑7. French. [CrossRef]

4. July J, Patricia D, Gunawan PY, Setiajaya H, Ginting TE, Putra TP, Wuisan Z, Budhiarko D, Masykura N, Prayogi G, Utomo AR, Tandean S, Loe ML. Clinicopathological associations and prognostic values of IDH1 gene mutation, MGMT gene promoter methylation, and PD-L1 expressions in high-grade glioma treated with standard treatment. Pan Afr Med J. 2020 Aug 20;36:309. [CrossRef] [PubMed] [PubMed Central]

5. Thomas DL. 2021 updates to the World Health Organization classification of adult-type and pediatric-type diffuse gliomas: a clinical practice review. Chin Clin Oncol. 2023 Feb;12(1):7. [CrossRef] [PubMed]

6. Takano S, Kato Y, Yamamoto T, Kaneko MK, Ishikawa E, Tsujimoto Y, Matsuda M, Nakai K, Yanagiya R, Morita S, Tsuboi K, Matsumura A. Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors. J Neurooncol. 2012 Jul;108(3):361-73. [CrossRef] [PubMed]

7. Lewandowska MA, Furtak J, Szylberg T, Roszkowski K, Windorbska W, Rytlewska J, Jóźwicki W. An analysis of the prognostic value of IDH1 (isocitrate dehydrogenase 1) mutation in Polish glioma patients. Mol Diagn Ther. 2014 Feb;18(1):45-53. [CrossRef] [PubMed] [PubMed Central]

8. Gondim DD, Gener MA, Curless KL, Cohen-Gadol AA, Hattab EM, Cheng L. Determining IDH-Mutational Status in Gliomas Using IDH1-R132H Antibody and Polymerase Chain Reaction. Appl Immunohistochem Mol Morphol. 2019 Nov/Dec;27(10):722-725. [CrossRef] [PubMed]

9. Gülten G, Yalçın N, Baltalarlı B, Doğu G, Acar F, Doğruel Y. The importance of IDH1, ATRX and WT-1 mutations in glioblastoma. Pol J Pathol. 2020;71(2):127-137. [CrossRef] [PubMed]

10. Capper D, Weissert S, Balss J, Habel A, Meyer J, Jäger D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010 Jan;20(1):245-54. [CrossRef] [PubMed] [PubMed Central]

11. Chen JR, Yao Y, Xu HZ, Qin ZY. Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas. Medicine (Baltimore). 2016 Mar;95(9):e2583. [CrossRef] [PubMed] [PubMed Central]

12. Miller JJ, Shih HA, Andronesi OC, Cahill DP. Isocitrate dehydrogenase-mutant glioma: Evolving clinical and therapeutic implications. Cancer. 2017 Dec 1;123(23):4535-4546. [CrossRef] [PubMed]

13. Larsen C. Anomalies génétiques et moléculaires des glioblastomes (GBM) [Genetic and molecular abnormalities of glioblastomas (GBM)]. Bull Cancer. 2010 Nov;97(11):1389-407. French. [CrossRef] [PubMed]

14. Molinaro AM, Taylor JW, Wiencke JK, Wrensch MR. Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol. 2019 Jul;15(7):405-417. [CrossRef] [PubMed] [PubMed Central]

15. Suh CH, Kim HS, Jung SC, Choi CG, Kim SJ. Imaging prediction of isocitrate dehydrogenase (IDH) mutation in patients with glioma: a systemic review and meta-analysis. Eur Radiol. 2019 Feb;29(2):745-758. [CrossRef] [PubMed]

16. Olar A, Raghunathan A, Albarracin CT, Aldape KD, Cahill DP 3rd, Powell SZ, Goodman JC, Fuller GN. Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults. Ann Diagn Pathol. 2012 Jun;16(3):161-70. [CrossRef] [PubMed]

17. Kizilbash SH, Giannini C, Voss JS, Decker PA, Jenkins RB, Hardie J, Laack NN, Parney IF, Uhm JH, Buckner JC. The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma. J Neurooncol. 2014 Oct;120(1):85-93. [CrossRef] [PubMed] [PubMed Central]

18. Cai J, Zhu P, Zhang C, Li Q, Wang Z, Li G, Wang G, Yang P, Li J, Han B, Jiang C, Sun Y, Jiang T. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget. 2016 Mar 29;7(13):16384-95. [CrossRef] [PubMed] [PubMed Central]

19. De Leeuw BI, Van Baarsen KM, Snijders TJ, Robe PAJT. Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis. Neurooncol Adv. 2019 Oct 1;1(1):vdz032. [CrossRef] [PubMed] [PubMed Central]

20. Wang XW, Ciccarino P, Rossetto M, Boisselier B, Marie Y, Desestret V, Gleize V, Mokhtari K, Sanson M, Labussière M. IDH mutations: genotype-phenotype correlation and prognostic impact. Biomed Res Int. 2014;2014:540236. [CrossRef] [PubMed] [PubMed Central]

21. Jakovlevs A, Vanags A, Gardovskis J, Strumfa I. Molecular classification of diffuse gliomas. Pol J Pathol. 2019;70(4):246-258. [CrossRef] [PubMed]

22. Stancheva G, Goranova T, Laleva M, Kamenova M, Mitkova A, Velinov N, Poptodorov G, Mitev V, Kaneva R, Gabrovsky N. IDH1/IDH2 but not TP53 mutations predict prognosis in Bulgarian glioblastoma patients. Biomed Res Int. 2014;2014:654727. [CrossRef] [PubMed] [PubMed Central]

23. Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 2008 Dec;116(6):597-602. [CrossRef] [PubMed]

24. Takami H, Yoshida A, Fukushima S, Arita H, Matsushita Y, Nakamura T, Ohno M, Miyakita Y, Shibui S, Narita Y, Ichimura K. Revisiting TP53 Mutations and Immunohistochemistry--A Comparative Study in 157 Diffuse Gliomas. Brain Pathol. 2015 May;25(3):256-65. [CrossRef] [PubMed] [PubMed Central]

25. 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 Aug;31(8):1208-14. [CrossRef] [PubMed] [PubMed Central]

26. Barresi V, Eccher A, Simbolo M, Cappellini R, Ricciardi GK, Calabria F, Cancedda M, Mazzarotto R, Bonetti B, Pinna G, Sala F, Ghimenton C, Scarpa A. Diffuse gliomas in patients aged 55 years or over: A suggestion for IDH mutation testing. Neuropathology. 2020 Feb;40(1):68-74. [CrossRef] [PubMed]

27. Rajmohan KS, Sugur HS, Shwetha SD, Ramesh A, Thennarasu K, Pandey P, Arivazhagan A, Santosh V. Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the 'integrated' diagnosis approach. J Clin Pathol. 2016 Aug;69(8):686-94. [CrossRef] [PubMed]

28. Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009 Sep 1;27(25):4150-4. [CrossRef] [PubMed]

Downloads

Published

2025-12-29

How to Cite

Zghal, M., Charfi, S., Siala, W., Graja, S., Kolsi, F., Ghribi, W., Ayedi, L., Boudawara, M. Z. ., Daoud, J., & Sellami Boudawara , T. (2025). Status and prognostic impact of IDH1 in adult grade 4 diffuse gliomas. Ukrainian Neurosurgical Journal, 31(4), 61–67. https://doi.org/10.25305/unj.333185

Issue

Section

Original articles