Background: IDH1 mutation shows diagnostic, prognostic, and predictive value in gliomas. Direct Sanger sequencing is considered the gold standard to detect IDH1 mutation. However, this technology is not available in most neuropathological centers in developing countries such as Indonesia. Immunohistochemistry (IHC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) have also been used to detect IDH1 mutation. This study aimed to compare DNA sequencing, IHC, and PCR-RFLP in detecting IDH1 mutations in gliomas. Methods: Research subjects were recruited from Dr. Sardjito Hospital. Genomic DNA was extracted from fresh or formalin-fixed paraffin-embedded samples of tumor tissue. DNA sequencing, PCR-RFLP and IHC were performed to detect IDH1 mutation. Sensitivity, specificity, and accuracy of PCR-RFLP and IHC were calculated by comparing them to DNA sequencing as the gold standard. Results: Among 61 recruited patients, 13 (21.3%) of them carried a mutation in codon 132 of the IDH1 gene, as shown by DNA sequencing. PCR-RFLP and DNA sequencing have a concordance value of 100%. Meanwhile, the concordance value between IDH1 R132H IHC and DNA sequencing was 96.7%. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy for PCR-RFLP were all 100%. On the other hand, the sensitivity, specificity, and accuracy of IHC were 92.3%, 97.9%, and 96.7%, respectively. Conclusion: This study showed that both PCR-RFLP and IHC have high accuracy in detecting IDH1 mutation. We recommend a combination of PCR-RFLP and IHC to detect IDH1 mutation in resource-limited settings.

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.

BACKGROUND: Excessive use of pesticides is known to cause neurotoxicity. Chronic effects of pesticide poisoning include neuropathy and tremors. AIM: This study aimed to determine the association between pesticide exposure and the occurrence of neurological signs and symptoms, especially neuropathy and tremor, in farmers. METHODS: This was a cross-sectional study. The study location was Seloprojo Village, Ngablak District, Magelang Regency, Central Java Province. Farmers as subjects were recruited to determine neuropathy using Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scoring. Tremor events were measured with Tremor Rating Scale (TRS). Cholinesterase levels were examined using venous blood samples to determine the level of pesticide poisoning. RESULTS: Of the 120 farmers studied, 68.3% experienced pesticide poisoning with cholinesterase levels below normal values. Weakness of the upper limb was found in 10 subjects (8.33%), while weakness of the lower limbs was found in 6 subjects (5%). There were 59.2% farmers who met the neuropathy criteria from the DNS score and those who met the neuropathic criteria from the DNE score were 6.7%. Tremor symptoms were found in 71.7% of the farmers. There was no significant association between cholinesterase levels and DNS score (p = 0.737), but there were significantly lower levels of cholinesterase (p = 0.046) in the neuropathy group measured with DNE score. There was no significant association between cholinesterase levels and TRS (p = 0.204). CONCLUSION: Cholinesterase levels were significantly associated with neuropathy incidence measured with DNE criteria but statistically not related to tremors in farmers exposed to pesticides.

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