An international study to increase concordance in Ki67 scoring
An international study to increase concordance in Ki67 scoring
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DOI：
10.1038/modpathol.2015.38
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发表时间：
2015-06-01
期刊：
影响因子：
7.5
通讯作者：
Nielsen, Torsten O.
中科院分区：
文献类型：
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作者：
Polley, Mei-Yin C.;YLeung, Samuel C.;Nielsen, Torsten O.
尽管Ki 67是乳腺癌中的重要生物标志物，但其缺乏评分标准化，这限制了其临床应用。我们之前的研究发现，当实验室使用他们自己的评分方法对中央染色的组织微阵列载玻片进行评分时，存在变异性。在目前的研究中，来自8个国家的16个实验室校准到特定的Ki 67评分方法，然后对50个中心MIB-1染色的组织微阵列病例进行评分。简单的说明规定了评分模式和染色阈值，用于确定染色肿瘤细胞的百分比。为了进行校准，实验室对18张基于网络的“训练”和“测试”图像进行了评分。软件跟踪对象选择和评分。校准成功预先规定为与参考值相比的评分均方根误差= 0.90。通过校准活动，实验室性能显示出不显著但有希望的改善趋势（平均均方根误差从0.6降至0.4，最大绝对偏差从1.6降至0.9;配对t检验：均方根误差P=0.07，最大绝对偏差P = 0.06）。对于组织微阵列评分，组内相关性估计值为0.94（95%可信区间：0.90-0.97），显著且显著地>0.70，这是预先设定的成功最低目标。一些差异仍然存在，包括临床相关临界值。在通过基于网络的工具校准到常见的评分方法后，实验室可以在中心染色的组织微阵列载玻片上实现Ki 67评分的高实验室间重现性。尽管这些数据可能令人鼓舞，表明有可能在病理学实验室之间标准化Ki 67评分，但临床上重要的差异仍然存在。在这种生物标志物被推荐用于临床之前，未来的研究将需要将这种方法扩展到活检和整个切片，考虑染色变异性，并与结果联系起来。
Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference = 0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.