Department of Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Brain Tumor Pathol. 2022 Jul;39(3):151-161. doi: 10.1007/s10014-022-00429-2. Epub 2022 Mar 29.
The 2021 WHO classification stratifies ependymoma (EPN) into nine molecular subgroups according to the anatomic locations which outperforms histological grading. We aimed at molecularly reclassifying 200 EPN using immunohistochemistry (IHC) and sequencing for ZFTA fusions in supratentorial (ST) EPN. Further, we assessed the utility of L1CAM, cyclinD1, and p65 markers in identifying ZFTA fusion. Demographic profiles, histologic features, molecular subgroups and clinical outcome were retrospectively analyzed. IHC for L1CAM, cyclinD1, p65, H3K27me3, and H3K27M and sequencing for ZFTA fusion were performed. ZFTA fusions were identified in 44.8% ST EPN. p65 displayed the highest specificity (93.8%), while L1CAM had the highest sensitivity (92.3%) in detecting ZFTA fusions. The negative predictive value approached 96.6% and sensitivity improved to 96.2% with combinatorial IHC (L1CAM, cyclinD1, p65). H3K27me3 loss (PF-A) was noted in 65% PF EPN. Our results provide evidence that a combination of two of three (L1CAM, p65, and cyclinD1) can be used as surrogate markers for predicting fusion. ZFTA fusion, and its surrogate markers in ST, and H3K27me3 and younger age (< 5 years) in PF showed significant correlation with PFS and OS on univariate and Kaplan-Meier analysis. On multivariate analysis, H3K27me3 loss and younger age group are associated with poor clinical outcome.
2021 年世卫组织分类根据解剖位置将室管膜瘤 (EPN) 分为九个分子亚组，优于组织学分级。我们旨在使用免疫组织化学 (IHC) 和测序对 200 例幕上 (ST) EPN 进行分子重新分类，以检测 ZFTA 融合。此外，我们评估了 L1CAM、cyclinD1 和 p65 标志物在识别 ZFTA 融合中的效用。回顾性分析了人口统计学特征、组织学特征、分子亚组和临床结果。进行了 L1CAM、cyclinD1、p65、H3K27me3 和 H3K27M 的 IHC 和 ZFTA 融合的测序。在 44.8%的 ST EPN 中发现了 ZFTA 融合。p65 在检测 ZFTA 融合方面具有最高的特异性 (93.8%)，而 L1CAM 具有最高的敏感性 (92.3%)。阴性预测值接近 96.6%，联合 IHC (L1CAM、cyclinD1、p65)可将敏感性提高至 96.2%。在 65%的 PF EPN 中观察到 H3K27me3 缺失 (PF-A)。我们的结果提供了证据，表明三种中的两种 (L1CAM、p65 和 cyclinD1) 的组合可以用作预测融合的替代标志物。在 ST 中，ZFTA 融合及其替代标志物以及 H3K27me3 和年龄较小 (<5 岁) 与单变量和 Kaplan-Meier 分析的 PFS 和 OS 显著相关。在多变量分析中，H3K27me3 缺失和年龄较小的组与不良临床结局相关。
