Mitogen-activated protein kinase (MAPK) pathway plays a major role in pediatric low-grade gliomas (pLGGs). Immunohistochemistry with mutant-specific antibody, VE1, has appeared to be the most affordable and rapidly deployable method to identify tumors with aberrant MAPK signaling pathway, by highlighting tumor with BRAF^V600E mutation. Nonetheless, positive staining cases but not associated with BRAF^V600E mutation are also seen. We analyzed 62 pLGGs for the two commonest genetic aberrations in MAPK pathway: KIAA1549-BRAF fusion, using reverse-transcriptase polymerase chain reaction, and BRAF^V600E mutation, using VE1 antibody and Sanger sequencing. We recorded a specificity and accuracy rate of 68.75% and 75%, respectively, for VE1, when strong cytoplasmic staining is observed. Interestingly, we observed that cells with ganglionic features frequently bind VE1 but not associated with BRAF^V600E mutation. Such observation was also confirmed in four cases of differentiating neuroblastoma. This false positive staining may serve as an important confounder in the interpretation of VE1 immunoreactivity with major therapeutic implication. It is important to confirm the presence of BRAF^V600E mutation by DNA-based method, especially in tumor entities not known to, or rarely harbor such mutations.

中文翻译：

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神经节细胞分化经常使VE1抗体染色：潜在的陷阱。

丝裂原激活的蛋白激酶（MAPK）途径在小儿低度神经胶质瘤（pLGGs）中起主要作用。通过突出显示带有BRAF ^V600E突变的肿瘤，用突变特异性抗体VE1进行的免疫组织化学似乎是鉴定具有异常MAPK信号通路的肿瘤的最经济，最快捷的方法。尽管如此，也可以看到染色阳性但与BRAF ^V600E突变无关的病例。我们分析了62个pLGGs在MAPK途径在两个最常见的遗传畸变：KIAA1549 - BRAF融合，使用逆转录酶聚合酶链式反应，和BRAF ^V600E使用VE1抗体和Sanger测序进行突变。当观察到强烈的细胞质染色时，我们记录的VE1特异性和准确率分别为68.75％和75％。有趣的是，我们观察到具有神经节特征的细胞经常结合VE1，但与BRAF ^V600E突变无关。在四例分化成神经母细胞瘤的病例中也证实了这种观察。这种假阳性染色可能在解释VE1免疫反应性和主要治疗意义上起重要作用。通过基于DNA的方法确认BRAF ^V600E突变的存在非常重要，尤其是在未知或很少携带此类突变的肿瘤实体中。