Quantitative evaluation of TP53 immunohistochemistry to predict gene mutations: lessons learnt from a series of colorectal carcinomas
Quantitative evaluation of TP53 immunohistochemistry to predict gene mutations: lessons learnt from a series of colorectal carcinomas
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DOI：
10.1016/j.humpath.2018.10.012
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发表时间：
2019-02-01
期刊：
影响因子：
3.3
通讯作者：
Huehns, Maja
中科院分区：
文献类型：
--
作者：
Prall, Friedrich;Huehns, Maja
这项研究探讨了TP53免疫组织化学作为基因测序的替代方法是否可以像最近报道的卵巢癌一样成功地应用于结直肠癌。对87个肿瘤的编码外显子2-11进行Sanger测序，在61个肿瘤中发现了65个突变。用Do-7抗体进行免疫组化。经免疫组化模式识别评价，44例为过表达者，20例为野生型；细胞质免疫染色完全缺失9例，细胞质免疫染色完全缺失4例。然而，对于10个肿瘤，不可能确定过表达和野生型免疫染色之间的区别（“不确定”）。对数字图像进行定量分析(i)使用QuPath确定免疫阳性细胞的百分比，（ii）使用WEKA分割获得量化肿瘤细胞核免疫染色强度的指标，数据呈连续分布，解释了某些情况下模式识别评估失败的原因。然后使用定量数据通过受体算子曲线分析来定义截止点，从而可以预测TP53基因的突变状态，两种方法的敏感性分别为0.89和0.95，特异性均为0.81。总之，通过一种专门的方法，TP53免疫组织化学可以很好地作为分子研究的替代方法。考虑到TP53基因突变在化疗决策中的潜在预测作用，TP53免疫组织化学可能与分子基因研究一起具有价值，甚至可能跨越不同的癌症。(C) 2018爱思唯尔公司版权所有。
This study addressed if TP53 immunohistochemistry as a surrogate method for gene sequencing could be applied to colorectal carcinomas as successfully as recently reported for ovarian cancers. Sanger sequencing of the coding exons 2-11 of 87 tumors yielded a total of 65 mutations in 61 of the tumors. lmmunohistochemistry was done with the Do-7 antibody. By a pattem recognition evaluation of immunohistochemistry, 44 cases were classified as "overexpressors" and 20 as having "wild-type" immunostaining; complete absence of or cytoplasmic immunostaining was seen in 9 and 4 cases, respectively. However, for 10 tumors, a confident distinction between overexpression and wild-type immunostaining was not possible ("indeterminates"). Quantitative analysis on digital images (i) using QuPath to determine the percentage of immunopositive cells and (ii) WEKA segmentation to obtain an index that quantified the intensities of tumor cells' nuclear immunostaining showed a continuous distribution of the data, explaining failure of assessment by pattern recognition in some cases. Quantitative data were then used to define cutoffs by receiver operator curve analysis, which allowed for predicting the mutational status of the TP53 gene with sensitivities of 0.89 and 0.95 for the 2 methods, respectively, and specificities of 0.81 for both. In conclusion, by a dedicated approach, TP53 immunohistochemistry works well as a surrogate method for molecular studies. Considering the potential predictive role of TP53 gene mutations in chemotherapy decisions, TP53 immunohistochemistry may be of value alongside with molecular gene studies, possibly even across different cancers. (C) 2018 Elsevier Inc. All rights reserved.