Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
Department of Molecular Diagnosis, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
Biomed Res Int. 2020 May 16;2020:1353284. doi: 10.1155/2020/1353284. eCollection 2020.
The latest WHO guideline of CNS tumor defined a RELA fusion-positive ependymoma type with extremely poor prognosis, and the expression of L1CAM was correlated well with the presence of RELA fusion. However, the L1CAM protein expression in large sample gliomas other than ependymoma, its relationship with the RELA gene and its prognostic significance remained unknown. We examined the expression of L1CAM in 565 glioma cases (WHO grade I-IV). The L1CAM IHC-positive cases were selected to test RELA fusion with FISH break-apart probes. L1CAM was positive in 109 cases (19.29%) of all 565 glioma cases, with 18.27% in low-grade gliomas and 19.84% in high-grade gliomas, respectively. Unlike ependymoma, L1CAM protein expression was not correlated with the C11orf95-RELA fusion gene in other gliomas, but it had correction with the patient age (older than 45-year-old, = 0.006), ATRX mutation ( = 0.003) and Ki67 ( = 0.007). High expression of L1CAM was an independent prognostic factor in our cohort. Further analysis demonstrated that L1CAM strong positive expression was significantly associated with poor prognosis in gliomas, both in our cohort ( < 0.001) and TCGA ( < 0.009) dataset. Although uncorrelated with C11orf95-RELA fusion, L1CAM was a significant poor prognostic marker in glioma patients. More aggressive treatment should be taken for these patients and L1CAM might be a promising therapeutic target in glioma.
世界卫生组织(WHO)中枢神经系统肿瘤最新指南将 RELA 融合阳性的室管膜瘤定义为预后极差的肿瘤类型,L1CAM 的表达与 RELA 融合密切相关。然而,在室管膜瘤以外的大样本脑胶质瘤中,L1CAM 蛋白的表达情况、与 RELA 基因的关系及其预后意义尚不清楚。我们检测了 565 例脑胶质瘤病例(WHO 分级 I-IV)中 L1CAM 的表达情况。选择 L1CAM IHC 阳性病例,用 FISH 分离探针检测 RELA 融合。在 565 例脑胶质瘤病例中,L1CAM 阳性病例为 109 例(19.29%),低级别胶质瘤为 18.27%,高级别胶质瘤为 19.84%。与室管膜瘤不同,L1CAM 蛋白表达与其他脑胶质瘤中的 C11orf95-RELA 融合基因无关,但与患者年龄(>45 岁, = 0.006)、 ATRX 突变( = 0.003)和 Ki67( = 0.007)相关。在我们的队列中,L1CAM 高表达是独立的预后因素。进一步分析表明,在我们的队列( < 0.001)和 TCGA( < 0.009)数据集,L1CAM 强阳性表达与胶质瘤患者的预后不良显著相关。尽管与 C11orf95-RELA 融合无关,但 L1CAM 是脑胶质瘤患者的一个显著不良预后标志物。这些患者应采取更积极的治疗措施,L1CAM 可能是脑胶质瘤有前途的治疗靶点。