免疫组织化学检测胶质母细胞瘤患者 MGMT 甲基化状态的诊断准确性。
Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma.
机构信息
Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Indonesia.
Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Indonesia.
出版信息
Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3803-3808. doi: 10.31557/APJCP.2021.22.12.3803.
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.
背景
O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）基因通过修复致突变的 DNA 损伤，防止 DNA 复制和转录中的错配。MGMT 是高级别和低级别脑胶质瘤基于高危临床情况的化疗预测生物标志物。它也可用于治疗决策，以预测新诊断的低级别胶质瘤复发中的超突变。MGMT 甲基化的金标准检查是聚合酶链反应（PCR）。然而，由于该技术在印度尼西亚尚未广泛用于日常实践，因此需要一种简单且更简单的方法，如免疫组织化学（IHC）作为替代检查。本研究旨在预测免疫组织化学（IHC）在检测胶质瘤中 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）甲基化状态中的诊断准确性。
方法
这是一项使用 2017 年 10 月至 2021 年 3 月间的福尔马林固定石蜡包埋（FFPE）组织样本的横断面研究。胶质瘤的诊断是基于临床、影像学和组织病理学发现。使用免疫组织化学和 PCR 技术研究 MGMT 甲基化状态。通过以 PCR 为金标准方法，分析 IHC 的诊断价值。通过接收者操作特征（ROC）曲线和 Youden 指数确定最佳阈值来确定 IHC 的阳性率。
结果
在 75 例检查的样本中，29 例（38.7%）患者存在甲基化。IHC 检测 MGMT 甲基化的灵敏度为 86.2%、特异性为 63.0%、阳性预测值为 59.5%、阴性预测值为 87.9%和准确性为 72.0%。AUC 为 0.746，表明具有中等诊断价值。基于 Youden 指数的 IHC 检查最佳阳性阈值为 10%。
结论
在缺乏 PCR 技术的资源有限的情况下，免疫组织化学检查可用于检测胶质瘤患者的 MGMT 甲基化状态。
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