Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population

Abstract

Background: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas.

Methods: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records.

Results: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival.

Conclusions: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia. <br />.

Keywords: Glioma; IDH; Indonesia; Prognosis; clinicopathological features.

Figure 1

Nucleotide Sequencing Results Showing Wild-Type (A) and Mutant (B) IDH1 Genes

Figure 2

qRT-PCR Showing the Amplification of Methylated MGMT Promoter (Green curve), Unmethylated MGMT Promoter (Blue Curve), and a COL2A1 Control (Red Curve). Examples of a glioma sample with (A) and without (B) MGMT promoter methylation

Figure 3

Kaplan-Meier Survival Analysis Demonstrating that IDH1-mutant Glioma Patients (Straight Line) had a Significantly Longer Overall Survival (p = 0.016; log-rank test).