Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, Sweden.
Department of Oncology and Pathology, Karolinska Institute, 17177 Stockholm, Sweden.
Biomolecules. 2021 Oct 30;11(11):1612. doi: 10.3390/biom11111612.
Ki67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in Breast Cancer Working Group (IKWG) for Ki67 scoring and to evaluate the prognostic potential of this platform in an independent cohort. Four algorithms were independently built by four pathologists based on our study cohort using an open-source digital image analysis (DIA) platform (QuPath) following the detailed guideline of the IKWG. The algorithms were applied on an ER+ breast cancer study cohort of 157 patients with 15 years of follow-up. The reference Ki67 score was obtained by a DIA algorithm trained on a subset of the study cohort. Intraclass correlation coefficient (ICC) was used to measure reproducibility. High interobserver reliability was reached with an ICC of 0.938 (CI: 0.920-0.952) among the algorithms and the reference standard. Comparing each machine-read score against relapse-free survival, the hazard ratios were similar (2.593-4.165) and showed independent prognostic potential ( ≤ 0.018, for all comparisons). In conclusion, we demonstrate high reproducibility and independent prognostic potential using the IKWG DIA instructions to score Ki67 in breast cancer. A prospective study is needed to assess the clinical utility of the IKWG DIA Ki67 instructions.
Ki67 是乳腺癌中具有重要预后和潜在预测价值的生物标志物。然而，缺乏标准化会阻碍其临床应用。在这项研究中，我们旨在研究病理学家在遵循国际乳腺癌 Ki67 工作组（IKWG）Ki67 评分指南时的可重复性，并评估该平台在独立队列中的预后潜力。四位病理学家根据我们的研究队列，使用开源数字图像分析（DIA）平台（QuPath），独立地根据 IKWG 的详细指南为四位病理学家建立了四个算法。该算法应用于一个 ER+乳腺癌研究队列，该队列包含 157 例患者，随访时间为 15 年。通过在研究队列的一个子集上训练的 DIA 算法获得参考 Ki67 评分。采用组内相关系数（ICC）来衡量可重复性。算法之间的 ICC 为 0.938（置信区间：0.920-0.952），观察者之间的可靠性很高。将每个机器读取的评分与无复发生存率进行比较，危险比相似（2.593-4.165），且具有独立的预后潜力（≤0.018，所有比较）。总之，我们使用 IKWG DIA 指南来对乳腺癌中的 Ki67 进行评分，证明了其具有很高的可重复性和独立的预后潜力。需要进行前瞻性研究来评估 IKWG DIA Ki67 指南的临床实用性。
