Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration
Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration
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DOI：
10.1038/npjbcancer.2016.14
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发表时间：
2016-05-18
影响因子：
5.9
通讯作者：
Dowsett, Mitch
中科院分区：
文献类型：
--
作者：
Leung, Samuel C. Y.;Nielsen, Torsten O.;Dowsett, Mitch
核增殖生物标志物Ki 67的病理分析在乳腺癌和其他癌症中具有多种潜在作用。然而，Ki 67免疫组织化学的免疫组织化学（IHC）检测的临床实用性受到不可接受的实验室间分析变异性的阻碍。国际Ki 67工作组进行了一系列研究，旨在减少这种变异性并改善Ki 67的评估。本研究试图评估是否可以接受的性能可以实现预染色芯切活检使用标准化的评分方法。对30例原发性ER+乳腺癌核心活检的切片进行Ki 67集中染色，并在11个国家的22个实验室中循环。每个实验室使用三种方法对Ki 67进行评分：（1）全局（4个视野，每个视野100个细胞）;（2）加权全局（与全局相同，但按总面积的估计百分比加权）;和（3）热点（500个细胞的单个视野）。组内相关系数（ICC），一种衡量实验室间一致性的指标，用于未加权整体方法（0.87; 95%可信区间（CI）：0.81-0.93）符合评分再现性的预定成功标准，而加权全局（0.87; 95% CI：0.7999-0.93）和热点方法（0.84; 95% CI：0.770.92）略微失败。对核心活检组织进行Ki 67 IHC分析的未加权总体评估符合预定的评分重现性成功标准。少数病例仍显示出较大的评分差异。建立外部质量评估计划可能会进一步改善实验室之间的一致性。需要进行额外评价，以评估适当样本队列的染色变异性和临床有效性。
Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81-0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999-0.93) and hot-spot methods (0.84; 95% CI: 0.770.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples.