Department of Pathology, University of Szeged, Szeged, Hungary.
Pathobiology. 2013;80(3):111-8. doi: 10.1159/000343795. Epub 2012 Dec 14.
The Ki-67 proliferation index has received an important role in treatment tailoring and molecular classification of estrogen receptor-positive breast carcinomas. The aim was to analyze the reproducibility of assessing proliferation on the basis of Ki-67 immunohistochemistry.
Thirty core biopsy samples of breast cancer patients were analyzed after immunostaining with B56, SP6 and MIB-1 monoclonal Ki-67 antibodies. All samples were evaluated twice and independently by 3 pathologists, with each observer performing his daily routine practice. The ratio of Ki-67-positive cells was estimated with 5% accuracy. Correlation was calculated for the results of each investigator for all pairs of antibodies and for the results of each antibody for all pairs of investigators. Ki-67 scores were divided into categories of either 4 quarters or into 3 groups reflecting the St. Gallen consensus recommendations with 15 and 30% as cutoff values. The reproducibility of classifying the tumors into these categories was assessed with ĸ statistics.
Altogether, 540 evaluations were made. Good to excellent correlation (Spearman's and Pearson's coefficient range 0.74-0.92 and 0.73-0.93, respectively) was noted for the pairwise comparison of antibodies by observer and of observers by antibody. The inter- and intraobserver reproducibility of the Ki-67 score classification into equal quarters (1-25, 26-50, 51-75 and 76-100%) or into 3 categories with cutoffs at 15 and 30% was fair to poor in the middle categories, but moderate to substantial in the low and high ranges. Interobserver differences in practice potentially impacted on less consistent classification.
Our results indicate that the three different Ki-67 antibodies tested do not substantially influence the reproducibility of the estimated proliferation rates. Although reproducibility is better in the clinically more relevant distinction of high versus low proliferation, without standardization, the current practice of Ki-67 assessment in many laboratories does not allow proper and consistent therapeutic decision-making.
Ki-67 增殖指数在雌激素受体阳性乳腺癌的治疗定制和分子分类中起着重要作用。本研究旨在分析基于 Ki-67 免疫组化评估增殖的可重复性。
对 30 例乳腺癌患者的核心活检样本进行 B56、SP6 和 MIB-1 单克隆 Ki-67 抗体免疫染色后进行分析。所有样本均由 3 名病理学家进行两次独立评估，每位观察者均按照日常工作惯例进行。Ki-67 阳性细胞的比例以 5%的精度进行估计。计算了每位观察者对所有抗体配对的结果以及每位抗体对所有观察者配对的结果的相关性。Ki-67 评分分为 4 个四分之一或分为 3 个组，反映圣加仑共识建议的 15%和 30%作为截止值。使用κ统计评估将肿瘤分类为这些类别的可重复性。
总共进行了 540 次评估。观察者之间和抗体之间的抗体配对以及观察者之间的抗体配对的相关性良好至优秀（Spearman 和 Pearson 系数范围分别为 0.74-0.92 和 0.73-0.93）。将 Ki-67 评分分类为相等的四分之一（1-25、26-50、51-75 和 76-100%）或分为 3 个类别，截止值为 15%和 30%的中间类别具有良好至中等的可重复性，但在低和高范围内具有中等至较大的可重复性。实践中的观察者间差异可能影响到不太一致的分类。
我们的研究结果表明，测试的三种不同的 Ki-67 抗体并没有显著影响估计的增殖率的可重复性。虽然在高与低增殖之间的临床更相关的区别中可重复性更好，但如果没有标准化，目前许多实验室的 Ki-67 评估实践并不能允许适当和一致的治疗决策。
