High Grade Gliomas (HGG) are most common types of primary brain tumor, characterized by poor prognosis and immune evasion properties. Molecular profiling of HGG patients may help clinicians in developing therapeutic strategies. However, molecular profiles of Indonesian patients are rarely studied. We investigated the prevalence of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and Isocitrate Dehydrogenase (IDH) mutation as a primary prognostic biomarkers for chemotherapy, as well as Epidermal Growth Factor Receptor (EGFR) and Tumor Protein 53 (TP53) Expressions to describe HGG molecular properties in indonesian patient cohort.
FFPE tumor samples from Siloam hospital (N = 43 patients) were analyzed using methylation Specific PCR, High Resolution melting PCR, and Direct sequencing to identify methylation of MGMT promoter and mutation of IDH gene. Immunohistochemistry staining methods were performed to analyze expressions of EGFR and TP53 proteins. Statistic analysis were used to describe its association with age groups and histological classification [Glioblastoma Multiforme (GBM) vs (Non-GBM) HGG].
Four samples were discarded from analysis due to lack of viable tumor cells. GBM cases made up 64% of total sample (25/39) with median age 53 years old. The MGMT methylation rate was 36% (9/25) and more frequent in non-GBM groups (31% vs 44%; GBM vs non-GBM respectively). IDH1 mutation (R132H) were detected in 15% patient (6/39) and significantly related with non-GBM case (p = 0.0163). TP53 and EGFR protein expressions were detected in 73.6% (28/38) and 34% (13/38) of sample respectively. TP53 expressions were found frequently in non-GBM patients, whereas EGFR was most common in GBM patients. Overall survival analyses showed patients with overexpressed p53 proteins had good prognosis (p = 0.012).
Our retrospective study revealed the MGMT promoter methylation (36%) and IDH mutation rates (15%) and patterns were consistent to common features of HGG. Moreover, frequent p53 expression in our non GBM cohort was consistent with secondary nature of HGG and was associated with good prognosis. Our study may help improving treatment strategy based on distinct biomolecular characteristics.
Clinical trial identification
Legal entity responsible for the study
Institutional Review Board, Stemcell And Cancer Institute, PT. Kalbe Farma TBKFunding
PT. Kalbe Farma, Tbk
PT. Kalbe Farma, Tbk
All authors have declared no conflicts of interest.