上皮样胶质母细胞瘤伴BRAF V600E突变的临床诊疗及预后分析

Clinical diagnosis and prognosis of epithelioid glioblastoma with BRAF V600E mutation

目的通过对伴有BRAF V600E突变的上皮样胶质母细胞瘤(E-GBM)的临床病理特征、免疫组化表达、分子特征及影像学特征分析,提高对伴有BRAF V600E突变的E-GBM的认识,为临床诊断、治疗和探讨疾病发生机制提供参考依据。方法收集中山大学肿瘤防治中心分子诊断科2016—2022年收治的8例经组织病理学及基因检测确诊为BRAF V600E突变的E-GBM患者,分析其临床、影像学特征及病理学特点,并结合相关文献复习。结果8例E-GBM患者中男性2例,女性6例,年龄15~70岁(平均年龄43岁)。免疫组化染色:GFAP、IDH1、Olig-2、BRAF、p53、ATRX、INI-1、EMA、Syn、Ki-67有不同程度的阳性。Sanger测序显示8例患者均为IDH1/2野生型,2例检出TERT基因启动子第228位点突变。荧光定量PCR显示8例患者均存在BRAF V600E突变,1例检出MGMT启动子甲基化。结论伴有BRAF V600E突变的E-GBM是一种侵袭性强、罕见的恶性神经系统肿瘤,在临床病理学和分子遗传学方面均具有相对一致的特征,包括其显著好发于年轻患者,女性居多,发生部位几乎全部位于大脑半球,其组织学类型以E-GBM最为常见等。

Objective To improve the understanding of epithelioid glioblastoma(E-GBM)with BRAF V600E mutation by studying the clinicopathological characteristics,immunohistochemical expression,molecular characteristics and imaging of E-GBM with BRAF V600E mutation,to provide reference for clinical diagnosis,treatment and pathogenesis.Methods Eight patients with epithelioid glioblastoma with BRAF V600E mutation diagnosed by histopathology and gene testing from 2016 to 2022 in the Molecular Diagnosis Department of Cancer Prevention and Treatment Center of Sun Yat sen University were collected,and their clinical,imaging and pathological characteristics were analyzed,and related literature was reviewed.Results Among the 8 patients with E-GBM,2 were male and 6 were female,aged 15-70 years(average age 43 years).Immunohistochemically,GFAP,IDH1,Olig2,BRAF,P53,ATRX,INI-1,EMA,synaptophysin,and Ki-67 were positive to varying degrees.Sanger sequencing showed that 8 patients were IDH1/2 wild-type,and 2 patients had mutation at site 228 of TERT gene promoter.Fluorescence quantitative PCR showed that BRAFV600E mutation existed in 8 patients,and MGMT promoter methylation was detected in 1 patient.Conclusion E-GBM with BRAF V600E mutation is a highly invasive and rare malignant tumor of the nervous system.It has relatively consistent characteristics in clinical pathology and molecular genetics,including its significant predilection in young patients,mostly women,almost all of its occurrence sites in the cerebral hemisphere,and its histological type most commonly is E-GBM.