Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer
Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer
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DOI：
10.1136/jcp.2006.044537
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Lugli, Alessandro
中科院分区：
文献类型：
--
作者：
Zlobec, Inti;Steele, Russell;Lugli, Alessandro
背景资料：用于确定通过免疫组织化学检测的生物标志物的阳性的截止分数通常是任意设置的，并且在报告之间变化。为了评价受试者工作特征（ROC）曲线分析在确定新型肿瘤标志物透明质酸介导运动受体（RHAMM）的临床重要截止评分中的性能，方法：采用免疫组化法检测1197例MMR阳性结直肠癌组织中RHAMM蛋白的表达，并与1197例MMR阳性结直肠癌进行比较。通过评价阳性肿瘤细胞的百分比，使用半定量评分法对免疫反应性进行评分。对T分期、N分期、肿瘤分级、血管浸润和生存率进行ROC曲线分析。选择从曲线到具有最大灵敏度和特异性的点（即点（0.0，1.0））的最短距离的评分作为截止评分，导致最大数量的肿瘤被正确分类为具有或不具有临床结果。为了确定所选择的截止分数的可靠性，100 bootstraped重复进行重新sampling data.Results：T分期，N分期，肿瘤分级和血管浸润的截止分数是100%，生存90%。最常选择的截止分数从100 resamples也是100%的T分期，N分期，肿瘤分级，血管浸润和90%的survival.Conclusions：ROC曲线分析可以作为一种替代方法，在选择和验证的截止分数确定免疫组化肿瘤阳性的临床相关阈值。
Background: Cut-off scores for determining positivity of biomarkers detected by immunohistochemistry are often set arbitrarily and vary between reports.Aims: To evaluate the performance of receiver operating characteristic (ROC) curve analysis in determining clinically important cut-off scores for a novel tumour marker, the receptor for hyaluronic acid mediated motility (RHAMM), and show the reproducibility of the selected cut-off scores in 1197 mismatch-repair (MMR) proficient colorectal cancers (CRC).Methods: Immunohistochemistry for RHAMM was performed using a tissue microarray of 1197 MMR-proficient CRC. Immunoreactivity was scored using a semi-quantitative scoring method by evaluating the percentage of positive tumour cells. ROC curve analysis was performed for T stage, N stage, tumour grade, vascular invasion and survival. The score with the shortest distance from the curve to the point with both maximum sensitivity and specificity, i.e. the point (0.0, 1.0), was selected as the cut-off score leading to the greatest number of tumours correctly classified as having or not having the clinical outcome. In order to determine the reliability of the selected cut-off scores, 100 bootstrapped replications were performed to resample the data.Results: The cut-off score for T stage, N stage, tumour grade and vascular invasion was 100% and that for survival 90%. The most frequently selected cut-off score from the 100 resamples was also 100% for T stage, N stage, tumour grade, and vascular invasion and 90% for survival.Conclusions: ROC curve analysis can be used as an alternative method in the selection and validation of cutoff scores for determining the clinically relevant threshold for immunohistochemical tumour positivity.