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

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Bayuangga, Halwan Fuad; Panggabean, Andre Stefanus; Argo, Ibnu Widya; Donurizki, Aditya Dwi; Shaleh, Sabillal; Wicaksono, Adiguno Suryo; Dananjoyo, Kusumo; Asmedi, Ahmad; Hartanto, Rachmat Andi

doi:10.31557/apjcp.2020.21.8.2287

Cited by 12 publications

(12 citation statements)

References 47 publications

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“…In the study conducted by Malueka et al ., which included 106 cases of gliomas, IDH mutations were identified in 21.7% of cases. [ 17 ] In the current study, IDH-1 mutations were identified in IDH mutation 64% Grade II tumors and only 5.1% of the Grade IV tumors. In the current study, this finding statistically correlated with the degree of anaplasia in the tumor.…”

Section: Discussionmentioning

confidence: 54%

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Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study

et al. 2021

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BACKGROUND: Diffuse gliomas in the adult population are the most common primary central nervous system (CNS) tumors. The World Health Organization incorporated isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion with histopathological features into an “integrated diagnosis” in the revised classification of tumors of CNS. These molecular subgroups of diffuse gliomas are found to stratify patients into prognostically distinct groups better than the histological classification. The objectives of the current study were to assess the frequency of IDH mutation, ATRX expression loss, p53 overexpression, and 1p/19q co-deletion detection in adult diffuse gliomas (Grade II, III, and IV) and to correlate them with clinicopathological and histopathological features. MATERIALS AND METHODS: The current study was a tertiary care hospital-based retrospective case series of 112 cases of adult diffuse gliomas. Immunohistochemistry (IHC)-based molecular detection was performed for IDH-1, ATRX, and p53 and fluorescent in situ hybridization (FISH) was performed for 1p/19q co-deletion detection. RESULTS: IDH-1 mutation was present in 30.4% ( n = 34/112) cases, ATRX expression was lost in 18% ( n = 19/104) cases, p53 was mutated in 39.3% ( n = 42/107) cases and 1p19q was co-deleted in 25% ( n = 4/16) cases. In the IDH1 mutant cases, with retained ATRX, FISH for 1p/19q co-deletion was performed and was co-deleted in four cases. CONCLUSION: The results of the present study indicate that IHC including IDH1/2, ATRX, and p53 is useful for the molecular classification of diffuse gliomas, which could be useful for the evaluation of prognosis, especially Grade III and II. Although the immunohistochemical approach does not replace genetic testing completely, it is a practical and powerful means of assessing molecular genetic changes. IDH mutations are the established markers of better prognosis in diffuse gliomas.

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Section: Discussionmentioning

confidence: 54%

“…This finding is contrary to the results obtained from the study conducted by Malueka et al . [ 17 ] Wherein the authors inferred that about 40% of Grade IV tumors harbored the IDH-1 mutations. In the current study, 94.9% of the Grade IV tumors were IDH-1 negative.…”

Section: Discussionmentioning

confidence: 99%

Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study

et al. 2021

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“…Lower Ki67 expression correlates with a longer lifespan. 13 According to this research, IDH1 mutations were reported in 76.1% of glioma patients. Subsequently, this examines and reports the inclusion of ATRX and GFAP markers in a Southeast Asian glioma population.…”

Section: Discussionmentioning

confidence: 74%

Immunohistochemical Expression of IDH1, ATRX, Ki67, GFAP, and Prognosis in Indonesian Glioma Patients

Priambada¹,

Arifin²,

Saputro³

et al. 2023

IJGM

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Background The current World Health Organization (WHO) 2021 classification of human glioma is based on key molecular biomarkers to define neoplastic entities. This review further delineates mutant IDH (isocitrate dehydrogenase) from wild-type IDH disease, a necessity given the large survival gap between mutant IDH and wild-type IDH tumors. In Indonesia, there are currently few reports on the distribution and significance of these mutations. Therefore, this research aims to determine the relationship between IDH mutations, as well as clinicopathological and prognostic factors in patients with gliomas. Other immunohistochemical markers including ATRX (alpha-thalassemia/mental retardation, X-linked), Ki67 and GFAP (glial fibrillary acidic protein) expression were also evaluated. Methods Forty-two glioma samples were collected from patients who underwent surgery at Dr. Kariadi General Hospital in Semarang, Central Java, Indonesia. Fresh and paraffin-embedded, formalin-fixed tissue samples were removed and sectioned for hematoxylin and eosin staining, immunohistochemistry, and IDH analysis of mutation. Medical records were used to collect clinicopathological and survival data. Results IDH1 mutations were discovered in 32 (76,1%) patients, and those with IDH1 mutation had longer overall survival when corresponded to patients with IDH1-wild-type. Lower expression of Ki67 was discovered to be very associated with a better prognosis. Conclusion IDH1 mutations status showed a significant relationship with prognosis in patients with glioma. Meanwhile, other markers (ATRX, Ki67, and GFAP) did not correlate with the prognosis.

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“…The DNA from fresh tissue samples was extracted using the Quick DNA FFPE MiniPrep Kit (Zymo Research, USA). The NanoVue Plus spectrophotometer (GE Healthcare Life Sciences, Pittsburgh, PA, USA) was used to estimate the recovered DNA (Malueka et al, 2020). The EZ DNA Methylation-Gold Kit (Zymo Research Cat o. D5005 Lot No.…”

Section: Polymerase Chain Reaction Examinationmentioning

confidence: 99%

“…The interpretation of methylated status was marked if the green curve was under red curve, while unmethylated status was interpreted if the blue curve was under red curve (Figure 2). The red curve serves as an internal control of COL2A1 (Malueka et al, 2020).…”

Section: Polymerase Chain Reaction Examinationmentioning

confidence: 99%

Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma

Sahara

Hartanto

Yoshuantari

et al. 2021

Asian Pac J Cancer Prev

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Background:The O6-methylguanine-DNA methyltransferase (MGMT) gene prevents mismatch in DNA replication and transcription by repairing mutagenic DNA lesions. MGMT is a predictor biomarker of chemotherapy in high-grade and low-grade gliomas based on high-risk clinical conditions. It also can be used for therapeutic decisions to predict hypermutation in recurrence in newly diagnosed low-grade gliomas. The gold standard examination for the methylation is Polymerase Chain Reaction (PCR). However, this technique is not widely available in Indonesia for daily practice. Thus, an uncomplicated and simpler method such as immunohistochemistry (IHC) is needed as an alternative examination. This study aimed to predict the diagnostic accuracy of immunohistochemistry (IHC) in detecting the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in glioma. Methods: This research was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) tissue samples of glioma patients, dating between October 2017 until March 2021. Diagnosis of glioma was established based on clinical, radiological, and histopathological findings. MGMT methylation status was investigated using the IHC and PCR techniques. Diagnostic value of IHC was analyzed, with PCR as a gold standard method. Optimum threshold to determine positivity of IHC was determined by the Area Under the Curve (AUC) on Receiver Operating Characteristics (ROC) curve and Youden index. Results: Among 75 samples examined, 29 (38.7%) patients were methylated. IHC detected MGMT methylation with sensitivity of 86.2%, specificity of 63.0%, positive predictive value of 59.5%, negative predictive value of 87.9% and accuracy of 72.0%. The AUC was 0.746, indicating moderate diagnostic value. Optimum positivity threshold of the IHC examination based on Youden Index was 10%. Conclusion: IHC examination can be used to detect MGMT methylation status of glioma patients in limited resources setting, where PCR technique is not available.

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

Cited by 12 publications

References 47 publications

Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study

Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study

Immunohistochemical Expression of IDH1, ATRX, Ki67, GFAP, and Prognosis in Indonesian Glioma Patients

Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma

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