Laboratory of Neural Reconstruction, Beijing Key Laboratory of Central Nervous System Injury.
Department of Neurosurgery, Beijing Tian Tan Hospital.
Am J Surg Pathol. 2021 Jul 1;45(7):979-987. doi: 10.1097/PAS.0000000000001669.
Adult intracranial ependymomas (EPNs) are extremely rare brain tumors. Currently, clinical and molecular factors that could inform individualized treatment strategies are still lacking for EPNs in this age group. The aim of this study was to investigate potential prognostic indicators and rational therapeutic management in a large cohort of adult intracranial EPNs. Adult patients who underwent resection of World Health Organization (WHO) grade II or III intracranial EPNs were included. The demographic features, clinicopathologic manifestations, molecular subgroups, and outcomes were retrospectively analyzed. Overall survival and progression-free survival were calculated using the Kaplan-Meier analysis. Potential prognostic indicators were identified using multivariable Cox proportional hazards model. This cohort included 236 adult patients with a mean age of 36.2 years (range: 18 to 72 y) at diagnosis. The tumor location was supratentorial (ST) in 102 (43.2%) and infratentorial in 134 (56.8%). Pathologic analysis revealed 43.1% of ST-EPNs with RELA fusion and 88.1% of posterior fossa ependymomas (PF-EPNs) with positive H3K27me3 staining. Gross total removal was achieved in 169 cases (71.6%). During follow-up, 97 (41.1%) patients had disease progression and 39 (16.5%) died. Kaplan-Meier analysis showed that patients with H3K27me3-positive PF-EPN had excellent survival, whereas patients with RELA fusion-positive ST-EPN or H3K27me3-negative PF-EPN had poor prognosis (progression-free survival: P=1.3E-16, overall survival: P=2.5E-12). Multivariate analysis showed that molecular subgroup, extent of resection, and Ki-67 index were strong independent prognostic indicators. In conclusion, our study provides essential information on the prognostic prediction of adult intracranial EPNs that will assist in establishing appropriate risk stratification and individualized treatment strategies in future clinical trials.
成人颅内室管膜瘤（EPNs）是极为罕见的脑肿瘤。目前，对于该年龄段的 EPNs，仍缺乏能够提供个性化治疗策略的临床和分子因素。本研究旨在调查一个大的成人颅内 EPN 队列中潜在的预后指标和合理的治疗管理方法。纳入接受手术切除的世卫组织（WHO）二级或三级颅内 EPN 的成年患者。回顾性分析了患者的人口统计学特征、临床病理学表现、分子亚群和结果。使用 Kaplan-Meier 分析计算总生存期和无进展生存期。使用多变量 Cox 比例风险模型确定潜在的预后指标。该队列包括 236 名平均年龄为 36.2 岁（范围：18 至 72 岁）的成年患者。肿瘤位置在幕上（ST）的 102 例（43.2%），幕下的 134 例（56.8%）。病理分析显示 43.1%的 ST-EPN 存在 RELA 融合，88.1%的后颅窝室管膜瘤（PF-EPN）存在 H3K27me3 阳性染色。169 例（71.6%）达到大体全切除。在随访期间，97 例（41.1%）患者发生疾病进展，39 例（16.5%）死亡。Kaplan-Meier 分析显示 H3K27me3 阳性的 PF-EPN 患者生存良好，而 RELA 融合阳性的 ST-EPN 或 H3K27me3 阴性的 PF-EPN 患者预后较差（无进展生存期：P=1.3E-16，总生存期：P=2.5E-12）。多变量分析表明，分子亚群、切除程度和 Ki-67 指数是独立的预后强预测指标。总之，本研究提供了关于成人颅内 EPN 预后预测的重要信息，这将有助于在未来的临床试验中建立适当的风险分层和个体化治疗策略。
