The detection of IDH mutations in patients with diffusely infiltrating malignant astrocytomas resulted in substantial modifications in the concept of WHO classification of these tumors. An important underlying observation was that patients with anaplastic astrocytomas (AA) without IDH mutation had a clinical course similar to that of patients with glioblastomas (GBM). The underlying observations of the German Glioma Network and NOA-04, however, were based on mixed patient cohorts. While most GBM patients received combined radiochemotherapy, patients with AA usually had radiotherapy or chemotherapy only. This intrinsic shortcoming of the study raised the question of whether patients with AA, IDH wildtype, WHO grade III, might have better prognosis if treated with combined radiochemotherapy than patients with GBM receiving the same combination therapy. Thus, the question remains whether the established histopathological grading criteria for malignant astrocytomas in the absence of an IDH mutation are still important if neither vascular proliferation nor necrosis are detectable. All patients in the cohort investigated here with the diagnosis of AA or GBM were subjected to a combined radiochemotherapy according to the Stupp protocol independently of the histopathological diagnosis. Thus, the analysis of these patients allows to clarify whether patients with AA, IDH wildtype, WHO grade III have a prognosis similar to that of GBM, IDH wildtype, WHO grade IV, even under equivalent therapeutic conditions. We determined the IDH1 and IDH2 status by sequencing, the MGMT status by pyrosequencing after bisulfite treatment and the EGFR status of the patients by FISH. In fact, the patients with the histopathological diagnosis of an AA IDH wild-type under similar aggressive therapy showed a comparable and therefore no better prognosis (median overall survival (mOS) 16 months) than patients with a GBM (mOS 13 months). Instead, patients with an AA and an IDH mutation receiving the same therapy had a mOS of 54 months. Thus, it can be concluded that in the absence of an IDH mutation, the established histopathological grading criteria 'necrosis' and 'vascular proliferation' actually lose their prognostic significance. If, on the other hand, patients with malignant astrocytomas and an IDH mutation are examined, there is still a difference between patients with necrosis and/or vascular proliferation and those whose tumors do not show such characteristics. Accordingly, in patients with malignant astrocytomas with IDH mutation it can be concluded that a histological differentiation between AA IDH mutated and GBM IDH mutated remains beneficial from a prognostic perspective.

中文翻译：

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IDH突变在间变性星形细胞瘤和胶质母细胞瘤患者中的预后作用。

在弥漫性浸润性恶性星形细胞瘤患者中检测到 IDH 突变导致对这些肿瘤的 WHO 分类概念进行了重大修改。一个重要的潜在观察结果是，无 IDH 突变的间变性星形细胞瘤 (AA) 患者的临床过程与胶质母细胞瘤 (GBM) 患者相似。然而，德国神经胶质瘤网络和 NOA-04 的基本观察是基于混合的患者队列。虽然大多数 GBM 患者接受了联合放化疗，但 AA 患者通常只接受放疗或化疗。该研究的这一内在缺陷提出了 AA、IDH 野生型、WHO III 级、如果接受联合放化疗治疗，可能比接受相同联合治疗的 GBM 患者预后更好。因此，如果既不能检测到血管增生也不能检测到坏死，那么在没有 IDH 突变的情况下，既定的恶性星形细胞瘤的组织病理学分级标准是否仍然重要。在此研究的队列中诊断为 AA 或 GBM 的所有患者均根据 Stupp 方案独立于组织病理学诊断进行联合放化疗。因此，对这些患者的分析可以阐明是否患有 AA、IDH 野生型、WHO III 级的患者具有与 GBM、IDH 野生型、WHO IV 级相似的预后，即使在相同的治疗条件下也是如此。我们通过测序确定了 IDH1 和 IDH2 的状态，亚硫酸氢盐治疗后焦磷酸测序的 MGMT 状态和 FISH 患者的 EGFR 状态。事实上，组织病理学诊断为 AA IDH 野生型的患者在类似的积极治疗下表现出与 GBM 患者（mOS 13 个月）相当的预后（中位总生存期 (mOS) 16 个月），因此没有更好的预后。相反，接受相同治疗的 AA 和 IDH 突变患者的 mOS 为 54 个月。因此，可以得出结论，在没有 IDH 突变的情况下，既定的组织病理学分级标准“坏死”和“血管增殖”实际上失去了它们的预后意义。另一方面，如果检查患有恶性星形细胞瘤和 IDH 突变的患者，有坏死和/或血管增生的患者与肿瘤没有表现出这些特征的患者之间仍然存在差异。因此，在具有 IDH 突变的恶性星形细胞瘤患者中，可以得出结论，从预后的角度来看，AA IDH 突变和 GBM IDH 突变之间的组织学分化仍然是有益的。