Background: We primarily investigated the prognostic role of CDKN2A homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. Materials: We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the IDH1/2 mutation and CDKN2A deletion using NGS analysis with ONCOaccuPanel®. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and MGMT promoter methylation status. Results: The mean follow-up duration was 27.5 months (range: 4.1–43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, IDH-mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, IDH-wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had CDKN2A deletions. The high-risk group with CDKN2A deletion regardless of IDH1/2 mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.078), IDH1/2 mutation (mutant vs. wildtype; HR 6.352), and CDKN2A deletion (absence vs. presence; HR 13.454) were associated with OS independently. Conclusions: The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.
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机译：背景： 我们主要研究了 CDKN2A 纯合缺失在 CNS WHO 4 级胶质瘤中的预后作用。此外，我们计划检查 4 级神经胶质瘤的传统预后因素并验证结果。材料： 我们对我们研究所的神经胶质瘤队列进行了回顾性分析。我们回顾了跨越 15 年的病历，并根据 2021 年 WHO 中枢神经系统肿瘤分类检查了病理切片以获得更新的诊断。我们使用 ONCOaccuPanel® 的 NGS 分析检测了 IDH1/2 突变和 CDKN2A 缺失。此外，我们检查了传统的预后因素，包括年龄、 WHO 体能状态、切除范围和 MGMT 启动子甲基化状态。结果： 平均随访时间为 27.5 个月 （范围： 4.1-43.5 个月），平均总生存期 （OS） 为 20.7 个月 （SD， ±1.759）。在排除 6 例病理样本状况不佳的患者后，共有 136 例根据先前 WHO 分类标准诊断的胶质母细胞瘤病例被新分类为 29 例 （21.3%） 星形细胞瘤、IDH 突变和 CNS WHO 4 级病例，以及 107 例 （78.7%） 胶质母细胞瘤、IDH 野生型和 CNS WHO 4 级病例。其中，61 例 （56.0%） 有 CDKN2A 缺失。无论 IDH1/2 突变如何，CDKN2A 缺失的高危组平均 OS 为 16.65 个月 （SD，±1.554），无 CDKN2A 缺失且有 IDH1/2 突变的中危组平均 OS 为 21.85 个月 （SD，±2。082），无 CDKN2A 缺失且有 IDH1/2 突变的低风险组平均 OS 为 33.38 个月 （SD，±2.946）。多因素分析显示，年龄 （≥50 岁 vs. <50 岁;HR 4.645）、WHO 绩效（0、1 对 2;HR 5.002）、切除范围（大体全切除与他人;HR 5.528），MGMT 启动子甲基化，（甲基化与未甲基化;HR 5.078）、IDH1/2 突变 （突变型与野生型;HR 6.352） 和 CDKN2A 缺失 （缺失 vs. 存在;HR 13.454） 与 OS 独立相关。结论： 本研究提示 CDKN2A 缺失在 CNS WHO 4 级胶质瘤中起着强大的预后作用。即使 CNS WHO 4 级神经胶质瘤具有突变的 IDH1/2，由于 CDKN2A 缺失，它们的临床结果也可能很差。
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