首页 > 期刊杂志 > 正文

BRAF VE1 Immunoreactivity Patterns in Epithelioid Glioblastomas Positive for BRAF V600E Mutation.

BRAF V600E突变阳性的上皮样胶质母细胞瘤中BRAF VE1的免疫反应类型

Kleinschmidt-DeMasters BK,Aisner DL,Foreman NK

Abstract

Epithelioid glioblastomas (E-GBMs) manifest BRAF V600E mutation in up to 50% of cases, compared with a small percentage of ordinary GBMs, suggesting that they are best considered variants rather than a different pattern of GBM. Availability of a targeted therapy, vemurafenib, may make testing BRAF status important for treatment. It is unclear whether BRAF VE1 immunohistochemistry (IHC) can substitute for Sanger sequencing in these tumors. BRAF VE1 IHC was correlated with Sanger sequencing results on our original cohort of E-GBMs, and then new E-GBM cases were tested with both techniques (n=20). Results were compared with those in similarly assessed giant cell GBMs, anaplastic pleomorphic xanthoastrocytomas. All tumors tested showed 1:1 correlation between BRAF V600E mutational results and IHC. However, heavy background immunostaining in some negatively mutated cases resulted in equivocal results that required repeat IHC testing and additional mutation testing using a different methodology to confirm lack of detectable BRAF mutation. Mutated/BRAF VE1 IHC E-GBMs and anaplastic pleomorphic xanthoastrocytomas tended to manifest strong, diffuse cytoplasmic immunoreactivity, compared with previously studied gangliogliomas, which demonstrate more intense immunoreactivity in the ganglion than in the glial tumor component. One of our E-GBM patients with initial gross total resection quickly recurred within 4 months, required a second resection, and then was placed on vemurafenib; she remains tumor free 21 months after second resection without neuroimaging evidence of residual disease, adding to the growing number of reports of successful treatment of BRAF-mutated glial tumors with drug. E-GBMs show good correlation between mutational status and IHC, albeit with limitations to IHC. E-GBMs can respond to targeted therapy.

摘要

高达50%的上皮样胶质母细胞瘤存在BRAFV600E突变,而普通胶质母细胞瘤则仅有一小部分存在这种突变,提示最好将上皮样胶质母细胞瘤理解为是一种变异体而不是胶质母细胞瘤的不同类型。靶向治疗药物维罗非尼的应用,使得评估BRAF基因突变状态变得非常重要。尚不清楚上皮样胶质母细胞瘤中BRAFVE1的免疫组化结果能否替代Sanger测序结果。在我们上皮样胶质母细胞瘤的最初数据中,BRAFVE1免疫组化结果与Sanger测序是相关的,接着新的病例也用这两种方法进行了检测(n=20)。检测结果与巨细胞胶质母细胞瘤和间变多形性黄色星形细胞瘤进行了比较。全部结果均表明测序和免疫组化结果是完全相关的。然而,在一些测序结果阴性的病例中免疫组化较深的染色背景会得出模棱两可的结论,这就需要重复进行免疫组化染色、并使用不同的方法进行突变检测以确认BRAF基因突变阴性。与之前研究的神经节神经胶质瘤相比较,BRAFVE1突变的上皮样胶质母细胞瘤和间变多形性黄色星形细胞瘤的免疫组化结果是弥漫且强的胞浆反应,而神经节神经胶质瘤中,神经节成分比肿瘤的胶质成分免疫组化着色更强。我们的一例上皮样胶质母细胞瘤病人在最初全切术后4个月便复发,然后进行了二次手术,并使用了维罗非尼。她在二次切除术之后保持了无瘤生存21个月,没有肿瘤残余的神经影像学证据。这增加了维罗非尼成功治疗BRAF突变的神经胶质肿瘤的案例。即使存在一定的局限性,上皮样胶质母细胞瘤BRAFV600E突变状态与免疫组化结果有很好的相关性。上皮样胶质母细胞瘤对靶向治疗有效。

full text

我要评论

0条评论