INTRODUCTION:

Brain tumors pose a substantial clinical challenge due to their high rates of morbidity and mortality, affecting individuals across all age groups. Gliomas, which arise from glial cells, are among the most prevalent and aggressive forms of primary brain tumors, accounting for roughly 30% of all brain tumors and 80% of malignant brain tumors worldwide. The outlook for glioma patients varies significantly based on the tumor’s histological grade and molecular profile. In recent years, the discovery of mutations in the Isocitrate Dehydrogenase (IDH) genes has transformed the classification and treatment of gliomas. IDH mutations, especially in IDH1 and IDH2, are now recognized as crucial molecular markers that provide important prognostic and therapeutic information. Gliomas with IDH mutations generally show improved survival rates and better responses to treatment compared to IDH wild-type gliomas^1,2.

Despite the growing body of international research, local data on glioma molecular profiles in Indonesia, particularly at tertiary referral centers like RSUD Dr. Saiful Anwar Malang, remains limited. As a developing country, Indonesia faces significant challenges in implementing advanced molecular diagnostics. Historically, glioma diagnoses were based solely on histopathological criteria, often classified as "Not Otherwise Specified" (NOS) due to the lack of biomolecular evaluation. Moreover, molecular testing, including IDH mutation analysis, is not covered by government insurance, limiting its accessibility. The introduction of IDH mutation testing represents a relatively new diagnostic tool in Indonesia, particularly in the research hospital's setting, marking a pivotal shift in glioma diagnosis and management.

Understanding the prevalence and implications of IDH mutations within a regional context is essential for optimizing diagnostic and therapeutic strategies. The integration of molecular diagnostics, such as IDH status, into routine clinical practice not only refines tumor classification but also guides treatment decisions, particularly in determining the use of targeted therapies and predicting disease progression³.

This descriptive study serves as a foundational investigation to bridge this gap by providing a comprehensive profile of IDH mutation status among glioma patients treated at RSUD Dr. Saiful Anwar from 2018 to 2024. By correlating IDH status with demographic factors, tumor types, and WHO grading, this research aims to enhance the understanding of glioma behavior in a regional population. Furthermore, the study sets the stage for future research exploring the relationship between clinical and radiological aspects and molecular profiles, aiming to assess their impact on treatment and prognosis. The findings are expected to inform clinical practice and contribute to the broader effort of personalizing glioma management in Indonesia.

MATERIAL AND METHODS:

Study Design:

This descriptive observational study analyzed the histopathological and molecular profiles of glioma patients treated at RSUD Dr. Saiful Anwar, Malang, from 2018 to 2024. The primary aim was to determine the distribution of Isocitrate Dehydrogenase (IDH) mutation status and its correlation with demographic characteristics, tumor histology, and World Health Organization (WHO) grading. Data were collected retrospectively from patient medical records and histopathological reports.

Study Population and Sample:

The study encompassed all patients diagnosed with gliomas within the specified study period. To be included, patients had to meet the following criteria: (1) a confirmed histopathological diagnosis of glioma, (2) documented IDH mutation status (categorized as wild-type, mutant, or non-specific), and (3) complete demographic and clinical data, including tumor histology and WHO grading. Patients with incomplete records or unknown IDH status were excluded from the study.

A total of 31 patients fulfilled the inclusion criteria, comprising 16 females (52%) and 15 males (48%). The patients’ ages ranged from 9 to 94 years, with a mean age of 52.35 years (±16) and a mode of 61 years, underscoring the higher prevalence of gliomas among older individuals.

Data Collection:

Data were extracted from hospital records, including variables such as age, sex, tumor type, IDH mutation status, and WHO grading. IDH status was determined using immunohistochemistry or molecular assays like PCR, targeting common mutations, particularly IDH1 R132H. Tumor classification followed the 2021 WHO guidelines, which integrate molecular markers for enhanced diagnostic precision^4,5.

Analysis Statistics:

Descriptive statistics were applied to summarize the data. Continuous variables, such as age, were presented as means, standard deviations, and ranges, while categorical variables, including tumor type and IDH status, were expressed as frequencies and percentages. Analysis focused on the prevalence and distribution of IDH mutations across tumor types and grades, using SPSS version 26 for data processing⁶.

Ethical Considerations:

Ethical clearance for this study was granted by the Health Research Ethics Committee of the Faculty of Medicine, Universitas Brawijaya, under approval number 170/EC/KEPK/06/2024. The research complied with the ethical principles established in the Declaration of Helsinki. To ensure patient privacy, all identifiable information was anonymized throughout the study. Any amendments to the research protocol or adverse events that occurred during the study were reported to the Ethics Committee in line with their regulations.

Results Summary:

The study analyzed 31 glioma cases, with glioblastoma being the most frequent type (65%) and astrocytoma accounting for 35%. IDH mutations were identified in 5 patients (16%), while 18 (58%) were IDH wild-type, associated with more aggressive tumors. Eight patients (26%) had non-specific IDH status. WHO grading revealed that 16 tumors (52%) were Grade IV, 7 (23%) were Grade III, and 8 (26%) were Grade II. These results highlight the predominance of high-grade gliomas and emphasize the role of IDH mutation testing in guiding prognosis and treatment. The detailed demographic and clinical characteristics are presented in Table 1.

Table 1: Demographic and Clinical Characteristics of Glioma Patients

Characteristic	Number (n)
Total Patients	31
Gender – Female	16
Gender – Male	15
Age – Mean (± SD)	52.35 (± 16)
Age – Min	9
Age – Max	94
Age – Mode	61
Glioblastoma	20
Astrocytoma	11
	IDH Wild-Type (n)	IDH Mutant (n)	IDH Non-Specific (n)
WHO Grade II	2	3	3
WHO Grade III	5	1	1
WHO Grade IV	11	1	4

DISCUSSION:

This study underscores the pivotal role of molecular diagnostics, particularly the status of Isocitrate Dehydrogenase (IDH) mutations, in understanding glioma development and enhancing clinical outcomes. Gliomas, especially glioblastomas, account for a substantial proportion of primary brain tumors worldwide, characterized by high morbidity and mortality rates. The research offers valuable insights into the demographic, histopathological, and molecular profiles of glioma patients treated at RSUD Dr. Saiful Anwar, highlighting the necessity of incorporating molecular markers into standard clinical practice.

Mutations in IDH1 and IDH2 are critical molecular changes in gliomas. These mutations result in the production of the oncometabolite 2-hydroxyglutarate, which disrupts normal cellular differentiation and promotes tumor development. In this study, IDH mutations were detected in 16% of gliomas, a lower frequency than global statistics, which typically report higher mutation rates in lower-grade gliomas (Grade II and III) and secondary glioblastomas. Gliomas with IDH mutations generally have a more favorable prognosis, with longer progression-free survival (PFS) and overall survival (OS) compared to those with IDH wild-type mutations^2,3. Conversely, 58% of patients in this cohort had IDH wild-type gliomas, which are more aggressive, showing rapid progression and poorer outcomes, particularly in Grade IV glioblastomas¹. The remaining 26% of cases had non-specific IDH status, likely reflecting instances where molecular testing was incomplete or unavailable. This highlights the need for comprehensive molecular diagnostic protocols to prevent underclassification and ensure accurate prognostic and therapeutic decision-making⁷.

The incorporation of molecular biomarkers, such as IDH mutations, has greatly enhanced glioma classification and management by providing detailed insights into tumor biology and facilitating personalized treatment approaches. Biomarkers play a vital role in diagnosing diseases, assessing prognosis, and guiding therapeutic decisions, as noted by Sahu et al.⁸. Their utility extends beyond diagnosis, contributing to drug development and the optimization of treatment regimens. In particular, IDH mutation status is a key biomarker that offers critical information on tumor aggressiveness, enabling the customization of therapeutic strategies.

The advent of immuno-oncology agents has broadened the scope of cancer treatments, especially for the more aggressive IDH wild-type gliomas. As highlighted by Dhakad et al., immunotherapies can serve as an adjunct to conventional treatments, potentially improving outcomes for patients who do not respond well to standard therapy options⁹. However, as Nath et al. caution, the implementation of these advanced therapies presents challenges, including the need to manage therapy-related toxicities effectively, emphasizing the importance of careful clinical monitoring¹⁰.

Utilizing non-invasive biomarkers, as highlighted by Kotelevets et al., can significantly improve the early detection and monitoring of gliomas, serving as a valuable complement to molecular diagnostics¹¹. This approach is in line with Boralkar et al.'s advocacy for evidence-based prescribing practices to fully leverage the advantages of molecular diagnostics, such as IDH testing¹².

Additionally, biomarkers are crucial for understanding stress-related pathophysiological mechanisms in glioma progression. Agustina et al. suggest that combining stress biomarkers with molecular diagnostics can offer a more comprehensive perspective on disease progression and inform patient management strategies¹³.

The integration of personalized medicine and advanced imaging technologies, as discussed by Swapnaa and Kumar and Mirfendereski et al., underscores the importance of combining molecular profiling with imaging to optimize glioma treatment^14,15. Techniques like diffusion-weighted imaging (DWI) provide enhanced visualization of tumor microenvironments, improving the monitoring of therapeutic responses. Finally, Pagar and Mahale, along with Dubey and Singh, highlight the necessity of a holistic, multimodal approach that incorporates molecular diagnostics, imaging, and traditional therapeutic methods to effectively manage gliomas^16,17.

Glioblastoma emerged as the most frequent tumor type in this study, accounting for 65% of cases. This aligns with global epidemiological data, which identify glioblastoma as the most common and aggressive primary brain tumor, representing approximately 15% of all intracranial neoplasms. Characterized by significant vascular proliferation, necrosis, and rapid progression, glioblastomas have a poor prognosis despite intensive treatment efforts¹⁸.

Astrocytomas, comprising 35% of cases, were the second most prevalent tumor type. These tumors span a spectrum from low-grade (Grade II) to high-grade (Grade III and IV) and demonstrate varied clinical behaviors. In this study, Grade II astrocytomas appeared more frequently than previously reported, while high-grade astrocytomas were less common compared to glioblastomas^19,20.

WHO grading revealed that Grade IV tumors constituted 52% of the cases, emphasizing the aggressive nature of the cases managed at RSUD Dr. Saiful Anwar. Grade III tumors were observed in 23% of cases, and Grade II tumors in 26%, reflecting a broader distribution of tumor malignancy. This high proportion of high-grade tumors may be attributed to the hospital's role as a tertiary care center, which typically receives referrals for advanced and complex cases^21,22.

The mean age of patients in this study was 52.35 years, with a peak at 61 years, highlighting that gliomas primarily affect middle-aged and older adults. This aligns with global trends, where glioblastoma incidence peaks between 45 and 70 years²³. However, the inclusion of younger patients in the cohort underscores that gliomas can occur across a broad age spectrum. Pediatric and adolescent gliomas exhibit distinct molecular and clinical behaviors compared to adult gliomas, necessitating age-specific diagnostic and therapeutic strategies²⁴.

Gender distribution in this study showed a slight female predominance (52%), which contrasts with some epidemiological data indicating a male predominance in gliomas. This discrepancy may be due to regional variations or sampling bias. Notably, meningiomas, which are not the focus of this study, are more prevalent in females, whereas glioblastomas and astrocytomas generally show male predominance¹.

IDH mutations are recognized as critical prognostic biomarkers in gliomas. Studies demonstrate that IDH-mutant gliomas have distinct metabolic and epigenetic profiles, which confer a survival advantage. These mutations are associated with reduced tumor aggressiveness and increased sensitivity to alkylating agents like temozolomide, a key drug in glioblastoma therapy²⁵. The favorable prognosis of IDH-mutant gliomas is also linked to their lower propensity for necrosis and more organized histopathological architecture compared to IDH wild-type tumors²⁶.

Furthermore, IDH mutations influence the tumor microenvironment by modulating hypoxia-inducible factor (HIF) pathways and altering immune cell infiltration. These changes not only affect tumor progression but also present potential therapeutic opportunities, such as targeting IDH-mutant pathways with specific inhibitors²⁷.

The integration of molecular diagnostics, particularly IDH mutation testing, is crucial for enhancing glioma classification and management. The 2021 WHO Classification of Tumors of the Central Nervous System underscores the importance of incorporating molecular markers alongside traditional histopathological assessments, representing a significant shift towards precision oncology. This study reinforces the need for adopting such classification frameworks, especially in resource-limited settings where molecular diagnostics are still evolving⁸.

From a therapeutic standpoint, IDH mutation status is a vital tool for tailoring treatment strategies. Patients with IDH-mutant gliomas often achieve favorable outcomes with less aggressive treatments, reducing the risk of treatment-related toxicity while maintaining long-term survival²⁸. Conversely, IDH wild-type gliomas, being more aggressive, require intensive multimodal therapies, potentially including experimental options such as immunotherapy and molecularly targeted agents²⁹.

The regional data provided by this study have significant implications for healthcare policy and resource allocation. The high prevalence of aggressive gliomas in this cohort highlights the urgent need to develop specialized neuro-oncology services. These should encompass advanced imaging, comprehensive molecular diagnostics, and multidisciplinary care teams to optimize patient outcomes³⁰.

Despite its valuable insights, this study has limitations. The single-center design and relatively small sample size may limit the generalizability of its findings. Moreover, the non-specific IDH category reflects gaps in molecular diagnostic capabilities, which could be mitigated through investment in advanced diagnostic technologies and standardized testing protocols³¹.

Future research should emphasize longitudinal studies to track disease progression and treatment responses. Multicenter collaborations could provide larger datasets to validate these findings and explore regional variations in glioma epidemiology. Additionally, developing cost-effective molecular diagnostic tools is essential for broader implementation in resource-constrained settings³².

CONCLUSION:

This study highlights the critical role of IDH mutation status in glioma classification, prognosis, and therapeutic decision-making. The findings demonstrate a high prevalence of aggressive gliomas, predominantly glioblastomas, with significant molecular heterogeneity. IDH-mutant gliomas, observed in 16% of cases, exhibit better prognostic outcomes, underscoring the importance of molecular profiling in refining diagnosis and guiding personalized treatment strategies. Conversely, IDH wild-type gliomas, which constituted 58% of cases, were associated with more aggressive behavior and poorer outcomes. The integration of molecular diagnostics, such as IDH testing, into routine clinical practice is essential for advancing precision oncology, particularly in resource-limited settings, where 26% of patients had non-specific IDH results. Future research should focus on expanding molecular diagnostic capabilities and exploring innovative therapeutic approaches to improve outcomes for glioma patients.

ACKNOWLEDGEMENT:

The authors would like to express their gratitude to the Faculty of Medicine, Universitas Brawijaya for funding this research. We also extend our sincere appreciation to Saiful Anwar General Hospital, Malang, Indonesia, for providing the necessary facilities and support throughout the study. Additionally, we acknowledge all patients and medical staff who contributed to this research.

CONFLICT OF INTEREST:

There is no conflict of interest amongst the authors.

REFERENCES:

1. Franceschi E, de Biase D, Pession A, Tosoni A, Paccapelo A, Visani M, et al. Survival outcomes in glioma patients with noncanonical IDH mutations: Beyond diagnostic improvements. J Clin Oncol. 2019. doi:10.1200/JCO.2019.37.15_SUPPL.2028

2. Ren F, Zhao Q, Huang L, Zheng Y, Li L, He Q, et al. The R132H mutation in IDH1 promotes the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis and is correlated with a better prognosis in gliomas. Immunol Cell Biol. 2019; 97. doi:10.1111/imcb.12225

3. Pappula AL, Rasheed S, Mirzaei G, Petreaca RC. A genome-wide profiling of glioma patients with an IDH1 mutation using the Catalogue of Somatic Mutations in Cancer database. Cancers (Basel). 2021; 13. doi:10.3390/cancers13174299

4. Juratli T, Zolal A, Stasik S, Pietzsch M, Eisenhofer G, Linn J, et al. IDH mutation prediction in glioma: A multimodal approach. Neuro Oncol. 2019. doi:10.1093/neuonc/noz175.547

5. Gondim DD, Gener M, Curless KL, Cohen-Gadol A, Hattab E, Cheng L. Determining IDH mutational status in gliomas using IDH1-R132H antibody and polymerase chain reaction. Appl Immunohistochem Mol Morphol. 2019; 27(10): 722-5. doi:10.1097/PAI.0000000000000702

6. Pan T, Su C, Tang W, Lin J, Lu S, Hong X. Combined texture analysis of dynamic contrast-enhanced MRI with histogram analysis of diffusion kurtosis imaging for predicting IDH mutational status in gliomas. Acta Radiol. 2023; 64(12): 2552-60. doi:10.1177/02841851231180291

7. Choi Y, et al. Fully automated hybrid approach to predict the IDH mutation status of gliomas via deep learning and radiomics. Neuro Oncol. 2020. doi:10.1093/neuonc/noaa177

8. Sahu P, Pinkalwar N, Dubey RD, Paroha S, Chatterjee S, Chatterjee T. Biomarkers: an emerging tool for diagnosis of a disease and drug development. Asian J Res Pharm Sci. 2011; 1(1): 9-16.

9. Dhakad GG, Shirsat SP, Tambe KP. Review on immuno-oncology agents for cancer therapy. Res J Pharmacol Pharmacodyn. 2022; 14(1): 47-52.

10. Nath L, Choudhury U, Lahkar M. A study about the pattern of adverse effects of various oncology drugs in a tertiary care hospital of North East India. Res J Pharmacol Pharmacodyn. 2022; 14(4): 208-12.

11. Kotelevets S, Chekh S, Karakotova Z. Modern possibilities of the use of non-invasive serological biomarkers severe in population studies. Res J Pharm Technol. 2019; 12(9): 4274-82.

12. Boralkar A, Bobhate P, Khairnar A. Prospective cross-sectional study in evaluation of prescribing pattern of doctors for oncology treatment. Res J Pharm Technol. 2011; 4(4): 634-7.

13. Agustina R, Lesmana R, Zakiyah N, Zahrah SN. The utilization of biomarkers in stress-related diseases. Liver. 2024; 16: 17.

14. Swapnaa B, Kumar SV. Personalized medicine—a novel approach in cancer therapy. Res J Pharm Technol. 2017; 10(1): 341-5.

15. Mirfendereski S, Shabani A, Rostamzadeh A, Fatehi D. Molecular imaging using by diffusion-weighted imaging of brain tumor through signal intensity: progress in molecular cancer imaging. Res J Pharm Technol. 2017; 10(6): 1767-71.

16. Pagar KR, Mahale MR. A review on brain tumour, etiology and treatment. Asian J Pharm Res. 2023; 13(1): 51-4.

17. Dubey A, Singh Y. Medicinal properties of Cinchona alkaloids—a brief review.

18. Berger T, Wen P, Lang-Orsini M, Chukwueke U. World Health Organization 2021 Classification of Central Nervous System Tumors and Implications for Therapy for Adult-Type Gliomas: A Review. JAMA Oncol. 2022. doi:10.1001/jamaoncol.2022.2844

19. Richardson T, Kumar A, Xing C, Hatanpaa K, Walker JM. Overcoming the Odds: Toward a Molecular Profile of Long-Term Survival in Glioblastoma. J Neuropathol Exp Neurol. 2020;79(10):1031-7. doi:10.1093/jnen/nlaa102

20. Molinari E, Curran OE, Grant R. Clinical importance of molecular markers of adult diffuse glioma. Pract Neurol. 2019; 19: 412-6. doi:10.1136/practneurol-2018-002116

21. Ghosh H, Patel R, Woodward E, et al. Contemporary Molecular Landscape, Survival, and Prognostic Factors in Over 4,000 Gliomas. Neuro Oncol. 2023. doi:10.1093/neuonc/noad179.0642

22. Tesileanu CMS, Dirven L, Wijnenga M, et al. Survival of diffuse astrocytic glioma, IDH1/2-wildtype, with molecular features of glioblastoma, WHO grade IV. Neuro Oncol. 2019. doi:10.1093/neuonc/noz200

23. Fan X, Yang M, Zhang X, Li H, Wan X, Liu Y, et al. Mutation profiling of gliomas based on sex, age, and family history. J Clin Oncol. 2023. doi:10.1200/jco.2023.41.16_suppl.e14041

24. Lim-Fat M, Vogelzang J, Woodward EL, et al. A multi-institutional comparative analysis of IDH-mutant gliomas across age groups. Neuro Oncol. 2020. doi:10.1093/neuonc/noaa215.329

25. Shen G, Wang R, Gao B, Zhang Z, Wu G, Pope W. MRI features and prognosis of gliomas associated with IDH1 mutation. Front Oncol. 2020. doi:10.3389/fonc.2020.00852

26. Jones P, Carroll KT, Koch M, et al. Isocitrate dehydrogenase mutations in low-grade gliomas correlate with prolonged survival in older patients. Neurosurgery. 2019. doi:10.1093/neuros/nyy149

27. Park Y, Park J, Ahn J, et al. Transcriptomic landscape of lower grade glioma based on age-related non-silent somatic mutations. Curr Oncol. 2021; 28(3): 210. doi:10.3390/curroncol28030210

28. Kayabolen A, Yilmaz E, Bagci-Onder T. IDH Mutations in Glioma: Double-Edged Sword in Clinical Applications? Biomedicines. 2021. doi:10.3390/biomedicines9070799

29. Richardson LG, et al. Implications of IDH Mutations on Immunotherapeutic Strategies for Malignant Glioma. Neurosurg Focus. 2022. doi:10.3171/2021.11.FOCUS21604

30. Pirozzi CJ, Yan H. The Implications of IDH Mutations for Cancer Development and Therapy. Nat Rev Clin Oncol. 2021. doi:10.1038/s41571-021-00521-0

31. Yuile A, et al. Implications of Concurrent IDH1 and IDH2 Mutations on Survival in Glioma. Curr Issues Mol Biol. 2022; 44(10): 348. doi:10.3390/cimb44100348

32. Nunno VD, et al. Non-Canonical IDH1 and IDH2 Mutations Are Associated with Improved Survival in Gliomas. Neuro Oncol. 2021. doi:10.1093/neuonc/noab196.467

Received on 15.11.2024 Revised on 08.03.2025

Accepted on 07.06.2025 Published on 08.11.2025

Available online from November 13, 2025

Research J. Pharmacy and Technology. 2025;18(11):5389-5394.

DOI: 10.52711/0974-360X.2025.00777

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.