(1) Background:MGMT(O-6-methylguanine-DNA methyltransferase) promoter methylation remains an important predictive biomarker in high-grade gliomas (HGGs). The influence of necrosis on the fidelity ofMGMTpromoter (MGMTp) hypermethylation testing is currently unknown. Therefore, our study aims to evaluate the effect of varying degrees of necrosis onMGMTp status, as determined by pyrosequencing, in a series of primary and recurrent HGGs; (2) Methods: Within each case, the most viable blocks (assigned as ‘true’ MGMTp status) and the most necrotic block were determined by histopathology review.MGMTp status was determined by pyrosequencing. Comparisons ofMGMTp status were made between the most viable and most necrotic blocks. (3) Results: 163 samples from 64 patients with HGGs were analyzed.MGMTp status was maintained in 84.6% of primary and 78.3% of recurrent HGGs between the most viable and necrotic blocks. A threshold of ≥60% tumor cellularity was established at whichMGMTp status was unaltered, irrespective of the degree of necrosis. (4) Conclusions:MGMTp methylation status, as determined by pyrosequencing, does not appear to be influenced by necrosis in the majority of cases at a cellularity of at least 60%. Further investigation into the role of intratumoral heterogeneity onMGMTp status will increase our understanding of this predictive marker.
(1) 背景：MGMT（O-6-甲基鸟嘌呤-DNA甲基转移酶）启动子甲基化仍是高级别胶质瘤（HGGs）的重要预测性生物标志物。目前尚不清楚坏死对MGMT启动子（MGMTp）高甲基化检测准确性的影响。因此，本研究旨在通过焦磷酸测序法，评估不同程度坏死对一系列原发性和复发性HGGs中MGMTp状态的影响；(2) 方法：通过组织病理学评估确定每个病例中活性最高的组织块（作为“真实”MGMTp状态）和坏死最严重的组织块。采用焦磷酸测序法测定MGMTp状态。比较活性最高与坏死最严重组织块之间的MGMTp状态差异。(3) 结果：共分析64例HGGs患者的163份样本。在活性最高与坏死最严重组织块之间，84.6%的原发性HGGs和78.3%的复发性HGGs保持MGMTp状态一致。研究确定当肿瘤细胞含量≥60%时，无论坏死程度如何，MGMTp状态均保持不变。(4) 结论：通过焦磷酸测序测定的MGMTp甲基化状态在大多数病例中不受坏死影响，前提是肿瘤细胞含量至少达到60%。进一步研究肿瘤内异质性对MGMTp状态的影响，将增进我们对这一预测性标志物的理解。
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