Revisiting TP53 Mutations and Immunohistochemistry-A Comparative Study in 157 Diffuse Gliomas
Revisiting TP53 Mutations and Immunohistochemistry-A Comparative Study in 157 Diffuse Gliomas
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DOI：
10.1111/bpa.12173
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发表时间：
2015-05-01
期刊：
影响因子：
6.4
通讯作者：
Ichimura, Koichi
中科院分区：
文献类型：
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作者：
Takami, Hirokazu;Yoshida, Akihiko;Ichimura, Koichi
p53免疫组织化学和TP 53突变状态之间的关联一直存在争议。本研究旨在重新评估p53免疫组化预测TP 53突变状态的有效性。共157例弥漫性神经胶质瘤（世界卫生组织分级II-IV）采用冷冻组织样本，通过TP 53外显子4至10的外显子逐个外显子DNA测序进行评估。在所有病例中，用p53抗体（DO-7）对成对福尔马林固定石蜡包埋材料进行免疫组化，评估反应的程度和强度。在66个样本中共检测到72个突变。它们包括60个错义突变，5个无义突变，4个缺失和3个剪接位点的改变。受试者工作特征曲线分析表明，强p53免疫反应性超过10%的细胞提供了最准确的预测突变。使用该临界值，55例免疫阳性病例中有52例携带突变，而102例免疫阴性病例中只有14例显示突变，敏感性和特异性分别为78.8%和96.7%。具有移码突变的肿瘤经常显示阴性免疫染色。由独立观察员进行的染色判读获得了相当的准确度。因此，我们建议p53免疫组化作为一个中等敏感性和高度特异性的标志物来预测TP 53突变。
The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re-evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grades II-IV) were assessed by exon-by-exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO-7) on paired formalin-fixed paraffin-embedded materials was assessed for the extent and intensity of reactivity in all cases. A total of 72 mutations were detected in 66 samples. They included 60 missense mutations, five nonsense mutations, four deletions and three alterations in the splicing sites. A receiver operating characteristic curve analysis revealed that strong p53 immunoreactivity in more than 10% of cells provided the most accurate prediction of mutation. Using this cutoff value, 52 of 55 immunopositive cases harbored a mutation, whereas only 14 of 102 immunonegative cases showed mutations, sensitivity and specificity being 78.8% and 96.7%. Tumors with frameshift mutations frequently showed negative immunostaining. Staining interpretation by an independent observer yielded comparable accuracy. We thus propose p53 immunohistochemistry as a moderately sensitive and highly specific marker to predict TP53 mutation.