BRAF-V600E突变蛋白VE1在脑肿瘤中的表达特点及其诊断价值  

Expression patterns of BRAF-V600E mutant protein VE1 and its diagnostic value in brain tumors

作　　者：李海南 范冲竹 成白洁 张振斌 向璇 李智 Li Hainan;Fan Chongzhu;Cheng Baijie;Zhang Zhenbin;Xiang Xuan;Li Zhi(Department of Pathology,Guangdong Sanjiu Brain Hospital,Guangzhou 510510,China;Department of Pathology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sun University,Guangzhou 510120,China)

机构地区：[1]广东三九脑科医院病理科,广州510510 [2]中山大学孙逸仙纪念医院病理科,广州510120

出　　处：《中华神经外科杂志》2025年第1期37-43,共7页Chinese Journal of Neurosurgery

基　　金：广东省医学科学技术研究基金(A2023377);广州市科技计划(2024A03J0521)。

摘　　要：目的探讨BRAF-V600E突变蛋白VE1在脑肿瘤中的表达特点及其诊断价值。方法回顾性收集2021年10月至2022年10月于广东三九脑科医院病理科行病理学检查的120例脑肿瘤患者的组织病理学标本。其中神经节细胞瘤(GC)/神经节细胞胶质瘤(GG)48例,胚胎发育不良性神经上皮肿瘤(DNT)17例,多形性黄色星形细胞瘤(PXA)11例,上皮样胶质母细胞瘤(E-GBM)12例,毛细胞型星形细胞瘤(PA)13例,乳头状颅咽管瘤(P-CPG)14例,造釉细胞型颅咽管瘤(A-CPG)5例。采用免疫组织化学(IHC)染色方法检测VE1蛋白的表达情况,根据其表达模式分为弥漫性阳性、单个细胞阳性、涂布状阳性及阴性;将弥漫性阳性和单个细胞阳性判读为VE1蛋白阳性结果(BRAF-V600E突变型),涂布状阳性和阴性判读为VE1蛋白阴性结果(BRAF-V600E野生型)。采用实时荧光定量PCR(RT-qPCR)法检测BRAF-V600E的类型。以RT-qPCR检测结果为标准,分析IHC染色方法评估BRAF-V600E类型的准确性。结果120例标本中,IHC染色结果显示,VE1蛋白呈弥漫性阳性表达55例(45.8%)、单个细胞阳性10例(8.3%)、涂布状阳性20例(16.7%)、阴性35例(29.2%);其中48例GC/GG中上述4种表达模式均存在一定比例,14例P-CPG中VE1均呈弥漫性阳性表达,5例A-CPG中VE1蛋白均呈阴性表达;10例单个肿瘤细胞VE1蛋白阳性者仅存在于GC/GG中;最终判定VE1蛋白阳性表达者65例,阴性者55例。RT-qPCR检测结果显示,120例标本中,BRAF-V600E突变型67例,野生型53例。其中GC/GG的BRAF-V600E突变率为75%(36/48),DNT的突变比例为2/17、PXA为7/11、E-GBM为7/12、PA为1/13,14例P-CPG均存在BRAF-V600E突变,5例A-CPG均未见BRAF-V600E突变。IHC检测结果与RT-qPCR检测结果的一致率为98.3%(118/120),其中2例不一致者均为涂布状阳性者。结论不同脑肿瘤中BRAF-V600E突变率不同;通过IHC染色法检测VE1蛋白判断BRAF-V600E突变与RT-qPCR检测结果符合率较高;但对于VE1蛋白呈涂布状阳性表达Objective To explore the expression characteristics and diagnostic value of BRAF-V600E mutant protein VE1 in various brain tumors.Methods The specimens of 120 patients with brain tumors who underwent pathological examination in the Department of Pathology,Guangdong Sanjiu Brain Hospital from October 2021 to October 2022 were retrospectively collected.Among them,there were 48 cases of gangliocytoma(GC)/ganglioglioma(GG),17 cases of dysembryonic neuroepithelial tumor(DNT),11 cases of pleomorphic xanthoastrocytoma(PXA),12 cases of epithelioid glioblastoma(E-GBM),and 13 cases of pilocytic astrocytoma(PA),14 cases of papillary craniopharyngiomas(P-CPG)and 5 cases of adamantinomatous craniopharyngiomas(A-CPG).Immunohistochemical(IHC)staining was used to detect the expression of VE1 protein,which was divided into diffuse positive,single tumor cell positive,uniform"coating"positivity and negative according to the expression characteristics.The diffuse positive and single tumor cell positive results were interpreted as VE1 protein positive results(BRAF-V600E mutant),and the uniform"coating"positivity and negative results were interpreted as VE1 protein negative results(BRAF-V600E wild type).Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the type of BRAF-V600E.The accuracy of the IHC staining method for evaluating BRAF-V600E type was analyzed based on the results of RT-qPCR.Results Among the 120 samples,IHC staining showed that VE1 protein was diffuse positive in 55 cases(45.8%),single tumor cell positive in 10 cases(8.3%),uniform"coating"positivity form in 20 cases(16.7%)and negative in 35 cases(29.2%).In 48 cases of GC/GGs,the above four expression features appeared in varying amounts,and all 14 cases of P-CPG were diffuse positive,and 5 cases of A-CPG were negative.All 10 cases of positive in single tumor cells were found in GC/GG.VE1 protein expression was positive in 65 cases and negative in 55 cases.The results of RT-qPCR showed that 67 of the 120 cases were BRAF-V600E mutant and 53 were

关 键 词：脑肿瘤 免疫组织化学 聚合酶链反应 BRAF-V600E突变蛋白VE1 

分 类 号：R73[医药卫生—肿瘤]