Isocitrate dehydrogenase (IDH)-mutant astrocytoma with microvascular proliferation, necrosis, CDKN2A/B homozygous deletion, or any combination of these features corresponds to World Health Organization grade 4 according to current criteria. However, the prognostic significance of CDKN2A hemizygous deletion in IDH-mutant astrocytoma is not well established. We undertook a comprehensive study that included assessments of histological and genetic approaches to prognosis for these tumors. Samples from a cohort of 114 patients with extended observation were subjected to histological review and molecular analysis. CDKN2A (9p21) deletion was detected by fluorescence in situ hybridization. Overall survival (OS) was calculated via Kaplan-Meier estimation using the log-rank test. Histological grade, Ki-67 index, and the extent of surgical resection correlated with the OS of IDH-mutant astrocytoma patients. Both CDKN2A homozygous deletion and hemizygous deletion were detectable. Patients with CDKN2A homozygous-deletion tumors had the poorest OS; those with CDKN2A hemizygous-deletion tumors had an intermediate OS (p < .001). We then established a novel grading system that combined CDKN2A homozygous and hemizygous deletions with histological grade; the combined grading system was an independent prognostic factor for IDH-mutant astrocytomas. We conclude that CDKN2A homozygous and hemizygous deletion should be combined in a grading system for IDH-mutant astrocytomas.

中文翻译：

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结合组织学分级和 CDKN2A 纯合和半合子缺失的新型分级系统来预测 IDH 突变型星形细胞瘤的预后

根据当前标准，具有微血管增殖、坏死、CDKN2A/B 纯合缺失或这些特征的任何组合的异柠檬酸脱氢酶 (IDH) 突变型星形细胞瘤对应于世界卫生组织 4 级。然而，CDKN2A 半合子缺失在 IDH 突变型星形细胞瘤中的预后意义尚未明确。我们进行了一项全面的研究，包括评估这些肿瘤预后的组织学和遗传学方法。对来自 114 名长期观察患者的样本进行了组织学检查和分子分析。通过荧光原位杂交检测 CDKN2A (9p21) 缺失。总生存期 (OS) 通过使用对数秩检验的 Kaplan-Meier 估计来计算。组织学分级、Ki-67指数和手术切除范围与IDH突变星形细胞瘤患者的OS相关。CDKN2A纯合缺失和半合缺失均可检测到。患有 CDKN2A 纯合性缺失肿瘤的患者 OS 最差；患有 CDKN2A 半合子缺失肿瘤的患者具有中间 OS (p < .001)。然后，我们建立了一个新的分级系统，将CDKN2A纯合子和半合子缺失与组织学分级相结合；联合分级系统是 IDH 突变型星形细胞瘤的独立预后因素。我们的结论是，CDKN2A 纯合子和半合子缺失应该结合在 IDH 突变星形细胞瘤的分级系统中。