Department of Radiology, NYU Grossman School of Medicine, New York, New York.
Department of Neurosurgery, NYU Grossman School of Medicine, New York, New York.
Clin Cancer Res. 2024 Aug 15;30(16):3512-3519. doi: 10.1158/1078-0432.CCR-24-0311.
DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification.
Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed.
The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052).
The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.
DNA 甲基化分析将异柠檬酸脱氢酶（IDH）突变型星形细胞瘤分为甲基化低级别和高级别组。我们根据 2021 年世界卫生组织分类，研究了 T2 液体衰减反转恢复（T2-FLAIR）失配信号在预测 DNA 甲基化级别和细胞周期蛋白依赖性激酶抑制剂 2A/B（CDKN2A/B）纯合缺失（IDH 突变型星形细胞瘤 4 级的分子生物标志物）方面的应用。
对 DNA 甲基化谱分类的 IDH 突变型星形细胞瘤的术前 MRI 扫描（n=71）由两名放射科医生独立评估 T2-FLAIR 失配信号。分析 T2-FLAIR 失配在预测甲基化级别、CDKN2A/B 状态、拷贝数变异和生存方面的诊断效用。
45 例甲基化低级别病例中有 21 例（46.7%）和 26 例甲基化高级别病例中有 1 例（3.9%）存在 T2-FLAIR 失配信号（P<0.001），特异性为 96.2%，阳性预测值为 95.5%，阴性预测值为 51.0%，用于预测低甲基化级别。T2-FLAIR 失配信号也与完整的 CDKN2A/B 状态显著相关（P=0.028），特异性为 87.5%，阳性预测值为 86.4%，阴性预测值为 42.9%。总体多变量 Cox 分析显示，保留的 CDKN2A/B 状态与无进展生存率相关（P=0.01）。对 CDKN2A/B 状态、拷贝数变异和甲基化级别几乎平分的组织学 3 级亚组进行多变量 Cox 分析，结果显示 DNA 甲基化级别与总生存率相关（P=0.045），CDKN2A/B 状态与无进展生存率相关（P=0.052）有趋势。
T2-FLAIR 失配信号对 IDH 突变型星形细胞瘤的低甲基化级别和完整的 CDKN2A/B 具有高度特异性。
