Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2020 Jan;33(1):47-56. doi: 10.1038/s41379-019-0329-2. Epub 2019 Aug 2.
Ependymomas show poor correlation between World Health Organization grade and clinical outcome. A subgroup of supratentorial ependymomas are characterized by C11orf95-RELA fusions, presumed to be secondary to chromothripsis of chromosome 11, resulting in constitutive activation of the NF-κB signaling pathway and overexpression of cyclin D1, p65, and L1 cell adhesion molecule (L1CAM). These RELA-fused ependymomas are recognized as a separate, molecularly defined World Health Organization entity and might be associated with poor clinical outcome. In this study, we show that immunohistochemistry for NF-κB signaling components, such as L1CAM, p65, and cyclin D1, can help distinguish RELA-fused from non-RELA-fused supratentorial ependymomas. Furthermore, these three markers can reliably differentiate RELA-fused ependymomas from a variety of histologic mimics. Lastly, we report that RELA-fused ependymomas may be associated with different chromosomal copy number changes and molecular alterations compared to their non-RELA-fused counterparts, providing additional insight into the genetic pathogenesis of these tumors and potential targets for directed therapies.
室管膜瘤的世界卫生组织分级与临床结果之间相关性较差。一组幕上室管膜瘤的特征是 C11orf95-RELA 融合，推测是由于 11 号染色体的染色体重排导致 NF-κB 信号通路的组成性激活和细胞周期蛋白 D1、p65 和 L1 细胞黏附分子 (L1CAM) 的过表达。这些 RELA 融合的室管膜瘤被认为是一种单独的、分子定义的世界卫生组织实体，可能与不良的临床结果有关。在这项研究中，我们表明，针对 NF-κB 信号成分（如 L1CAM、p65 和细胞周期蛋白 D1）的免疫组化可以帮助区分 RELA 融合与非 RELA 融合的幕上室管膜瘤。此外，这三个标志物可以可靠地区分 RELA 融合的室管膜瘤与各种组织学模拟物。最后，我们报告 RELA 融合的室管膜瘤可能与非 RELA 融合的室管膜瘤相比存在不同的染色体拷贝数变化和分子改变，这为这些肿瘤的遗传发病机制和靶向治疗的潜在靶点提供了更多的见解。
