有丝分裂计数对 IDH 突变型星形细胞瘤具有预后意义，而 CDKN2A/B 杂合缺失则不然。EORTC 试验 26053（CATNON）和 EORTC 试验 22033-26033 共识小组审查结果。

Mitotic count is prognostic in IDH mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trial 26053 (CATNON) and EORTC trial 22033-26033.

机构信息

Department of Pathology, Laboratory for Tumor Immunopathology, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

Department of Neuropathology, University Hospital Zurich, University of Zurich, Switzerland.

出版信息

Neuro Oncol. 2023 Aug 3;25(8):1443-1449. doi: 10.1093/neuonc/noac282.

DOI:10.1093/neuonc/noac282

PMID:36571817

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10398806/

Abstract

BACKGROUND

Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas.

METHODS

An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) histologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power.

RESULTS

Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm2) significantly influences PFS (P = .0098) and marginally the OS (P = .07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data.

CONCLUSION

The mitotic index (cut-off 2 per 10 40× HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status.

摘要

背景

具有 IDH1/2 突变但无 1p19q 缺失的神经胶质瘤已被确定为 IDH 突变型星形细胞瘤（IDHmut 星形细胞瘤）的独特诊断实体。最近，细胞周期蛋白依赖性激酶 4 抑制剂 A/B（CDKN2A/B）的纯合缺失已被纳入这些肿瘤的分级。组织学参数是否除了分子分类外，还能提供预后信息，这个问题尚未得到解答。在这里，我们评估了共识组织学参数，以在 IDHmut 星形细胞瘤中提供额外的预后价值。

方法

一个由 7 名神经病理学家组成的国际小组对来自 EORTC 试验 22033-26033（低级别胶质瘤）的 192 例 IDHmut 星形细胞瘤和 EORTC 26053（CATNON）（1p19q 未缺失的间变性神经胶质瘤）的 263 例虚拟显微镜图像中的 13 个明确的组织学特征进行了评分。对于 192 例神经胶质瘤，已知 CDKN2A/B 状态。共识（≥4/7 位小组成员的一致）组织学特征与 CDKN2A/B 的纯合缺失（HD）一起进行测试，以评估其独立的预后能力。

结果

在共识组织学参数中，有丝分裂计数（标准化为每 10 个高倍视野有 2 个有丝分裂，视野直径为 0.55 毫米，面积为 0.24 平方毫米）显著影响无 HD CDKN2A/B 的患者的 PFS（P=0.0098）和 OS（P=0.07）。有丝分裂计数也显著影响 HD CDKN2A/B 的肿瘤的 PFS，但对 OS 的影响不大，可能是因为随访数据有限。