Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. H3K27me3 immunostaining was performed in 69 diffuse gliomas with oligodendroglial (n = 62) or oligoastrocytic (n = 7) morphology. The integration with routinely assessed IDH mutations, ATRX immunostaining, and 1p/19q codeletion classified these cases as 60 oligodendroglial and 9 astrocytic. H3K27me3 was lost in 58/60 oligodendrogliomas with retained (n = 47) or non-conclusive (n = 11) ATRX staining, 3/6 IDH-mutant astrocytomas with ATRX loss, and 3/3 IDH-wt astrocytomas. H3K27me3 was retained in 2/60 oligodendrogliomas with retained ATRX, and in 3/6 IDH-mutant astrocytomas, two of which had lost and one retained ATRX. The combination of H3K27me3 and ATRX immunostainings with IDH mutational status correctly classified 55/69 (80%) cases. In IDH-mutant gliomas, ATRX loss indicates astrocytic phenotype, while ATRX retention and H3K27me3 loss identify oligodendroglial phenotype. Only 14 (20%) IDH-mutant cases with retained ATRX and H3K27me3 or inconclusive ATRX immunostaining would have requested 1p/19q codeletion testing to be classified. Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.

少突胶质细胞瘤由IDH突变和 1p/19q 共缺失定义。后者与 ATRX 免疫组织化学损失相互排斥，并且最近与 H3K27me3 免疫染色的损失有关。我们旨在评估 H3K27me3 免疫表达在具有少突胶质细胞或混合少突胶质细胞形态的弥漫性胶质瘤中的诊断和预后价值。在 69 个具有少突胶质细胞 (n = 62) 或少突星形细胞 (n = 7) 形态的弥漫性胶质瘤中进行 H3K27me3 免疫染色。与常规评估的IDH突变、ATRX 免疫染色和 1p/19q 共缺失的整合将这些病例分类为 60 个少突胶质细胞和 9 个星形胶质细胞。H3K27me3 在 58/60 少突胶质细胞瘤中丢失，保留 (n = 47) 或非结论性 (n = 11) ATRX 染色，3/6 IDH- 具有 ATRX 丢失的突变星形细胞瘤和 3/3 IDH -wt 星形细胞瘤。H3K27me3 保留在 2/60 保留 ATRX 的少突胶质细胞瘤和 3/6 IDH突变星形细胞瘤中，其中两个丢失，一个保留 ATRX。H3K27me3 和 ATRX 免疫染色与IDH突变状态的组合正确分类了 55/69 (80%) 病例。在IDH突变型神经胶质瘤中，ATRX 缺失表明星形细胞表型，而 ATRX 保留和 H3K27me3 缺失表明少突胶质细胞表型。只有 14 (20%) 个IDH-具有保留 ATRX 和 H3K27me3 或不确定的 ATRX 免疫染色的突变病例将要求对 1p/19q 共缺失测试进行分类。此外，H3K27me3 保留与显着更短的无复发生存期相关（P < 0.0001），独立于IDH突变或 1p/19q 共缺失（P < 0.005）。我们的数据表明，将 H3K27me3 免疫染色添加到具有少突胶质细胞或混合形态的弥漫性胶质瘤的诊断工作流程中有助于大幅减少需要 1p/19q 共缺失测试的病例数量并提供相关的预后信息。