Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology-Council of Scientific and Industrial Research (IGIB-CSIR), New Delhi, India.
J Neurooncol. 2018 May;138(1):29-39. doi: 10.1007/s11060-018-2767-y. Epub 2018 Jan 22.
Ependymomas (EPN) show site specific genetic alterations and a recent DNA methylation profiling study identified nine molecular subgroups. C11orf95-RELA and YAP1 fusions characterise the RELA and YAP1 molecular subgroups, respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular subgrouping over histological grade for accurate prognostication. Clinicopathological features of ST-EPNs in correlation with C11orf95-RELA and YAP1 fusions have been assessed in only few studies. We aimed to study these fusions in EPNs, and identify diagnostic and prognostic markers. qRT-PCR and Sanger Sequencing for the detection of C11orf95-RELA, YAP1-MAMLD1 and YAP1-FAM118B fusion transcripts, gene expression analysis for NFKB1, and immunohistochemistry for p53, MIB-1, nestin, VEGF, and L1CAM were performed. 88 EPNs (10-Grade I and 78-Grade II/III) from all sites were included. RELA fusions were unique to Grade II/III ST-EPNs, detected in 81.4% (22/27) and 18.5% (5/27) of pediatric and adult ST-EPNs respectively. ST-EPNs harbouring RELA fusions showed frequent grade III histology (81.5%), clear cell morphology (70.3%), upregulated NFKB1 expression, MIB-1 labelling indices (LI) ≥ 10% (77.8%), and immunopositivity for nestin (95.7%), VEGF (72%), L1CAM (79%), and p53 (64%). Presence of RELA fusions, L1CAM immunopositivity and MIB-1 LI ≥ 10% associated with poor outcome. L1CAM showed 81% concordance with RELA fusions. YAP1-MAMLD1 fusion was identified in a single RELA fusion negative adult anaplastic ST-EPN. RELA fusions are frequent in ST-EPNs and associate with poor outcome. L1CAM is a surrogate immunohistochemical marker. RELA fusion positive ST-EPNs strongly express nestin indicating increased stemness. Further evaluation of the interactions between NFKB and stem cell pathways is warranted.
室管膜瘤（EPN）表现出特定部位的遗传改变，最近的 DNA 甲基化分析研究确定了 9 个分子亚群。C11orf95-RELA 和 YAP1 融合分别代表幕上（ST）-EPN 的 RELA 和 YAP1 分子亚群。目前的指南建议根据分子亚群而不是组织学分级进行预后评估。仅有少数研究评估了 ST-EPN 的临床病理特征与 C11orf95-RELA 和 YAP1 融合之间的关系。我们旨在研究这些融合在 EPN 中的作用，并确定诊断和预后标志物。采用 qRT-PCR 和 Sanger 测序检测 C11orf95-RELA、YAP1-MAMLD1 和 YAP1-FAM118B 融合转录本，进行 NFKB1 基因表达分析，以及免疫组织化学检测 p53、MIB-1、巢蛋白、VEGF 和 L1CAM。纳入了来自所有部位的 88 例 EPN（10 例 I 级和 78 例 II/III 级）。RELA 融合仅存在于 II/III 级 ST-EPN，在儿科和成人 ST-EPN 中分别检测到 81.4%（22/27）和 18.5%（5/27）。携带 RELA 融合的 ST-EPN 常表现为 III 级组织学（81.5%）、透明细胞形态（70.3%）、NFKB1 表达上调、MIB-1 标记指数（LI）≥10%（77.8%）、巢蛋白（95.7%）、VEGF（72%）、L1CAM（79%）和 p53（64%）免疫阳性。存在 RELA 融合、L1CAM 免疫阳性和 MIB-1 LI≥10%与不良预后相关。L1CAM 与 RELA 融合的一致性为 81%。YAP1-MAMLD1 融合仅在 1 例 RELA 融合阴性成人间变性 ST-EPN 中被识别。RELA 融合在 ST-EPN 中很常见，并与不良预后相关。L1CAM 是一种替代的免疫组织化学标志物。RELA 融合阳性 ST-EPN 强烈表达巢蛋白，表明干性增加。进一步评估 NFKB 和干细胞途径之间的相互作用是必要的。
