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

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.

Case series of cutaneous Langerhans cell histiocytosis in Indonesian children; The clinicopathological spectrum.

Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by the clonal proliferation of Langerhans cells, which are immunoreactive to S-100 and CD-1a/ CD207 (Langerin). Cutaneous involvement is the most common presentation of LCH in children. It is suggested that the patients with single-system LCH limited to the skin have a better prognosis than those with systemic involvement. Three histologic reactions of cutaneous LCH have been reported and are associated with the clinical types of LCH. These histological reactions include: proliferative, granulomatous, and xanthomatous. This study presents the clinicopathological features of ten cutaneous LCH cases collected from Dr. Sardjito General Hospital Yogyakarta Indonesia between 2014-2018. The ten cases showed various clinical features, in which some features mimic other diseases. The microscopic features of skin biopsies showed granulomatous reaction in 80% of cases and proliferative reaction in the other 20%. Five patients (50% of cases) who died had systemic manifestation of thrombocytopenia, anemia, icterus, hepatosplenomegaly, and revealed the granulomatous type from their skin biopsy specimens. The clinical recognition of LCH and subsequent histological reaction determination are important since some cases may develop multisystem disease and have a poor prognosis.