Standardized Ki67 Diagnostics Using Automated Scoring-Clinical Validation in the GeparTrio Breast Cancer Study
Standardized Ki67 Diagnostics Using Automated Scoring-Clinical Validation in the GeparTrio Breast Cancer Study
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DOI：
10.1158/1078-0432.ccr-14-1283
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发表时间：
2015-08-15
影响因子：
11.5
通讯作者：
von Minckwitz, Gunter
中科院分区：
文献类型：
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作者：
Klauschen, Frederick;Wienert, Stephan;von Minckwitz, Gunter
目的：通过Ki 67免疫组化对增殖进行评分是预测乳腺癌患者对化疗的治疗反应的重要组成部分。然而，最近的研究对多中心环境中“视觉”Ki 67评分的可靠性提出了质疑，特别是在较低但具有临床重要性的增殖范围内。因此，一个准确的和标准化的Ki 67评分是至关重要的，无论是在常规诊断和大型多中心studies.Experimental设计：我们验证了一种新的全自动Ki 67评分方法，只依赖于最小的先验知识的细胞属性，不需要训练数据进行校准。我们将我们的方法应用于新辅助GeparTrio试验的1，082例乳腺癌样本，并比较了自动和手动Ki 67 scoring.Results的性能：三组autoKi 67定义为低（35%）自动评分显示pCR率分别为5.8%，16.9%和29.5%。AutoKi 67与预后显著相关，总体和无进展生存P值P-OS < 0.0001和P-PFS < 0.0002，而手动Ki 67评分的P-OS < 0.0005和P-PFS < 0.0001。此外，Ki 67自动评分是多变量分析中的独立预测因子，P-OS = 0.002，P-PFS = 0.009（autoKi67）vs P-OS = 0.007，P-PFS = 0.004（手动Ki 67）。结论：电脑-本文提出的辅助Ki 67评分方法提供了一种标准化的乳腺癌肿瘤细胞增殖评估方法，临床终点，并可用于常规诊断。因此，它可能有助于解决最近报告的Ki 67诊断的可靠性问题。（C）2014年AACR。
Purpose: Scoring proliferation through Ki67 immunohistochemistry is an important component in predicting therapy response to chemotherapy in patients with breast cancer. However, recent studies have cast doubt on the reliability of "visual" Ki67 scoring in the multicenter setting, particularly in the lower, yet clinically important, proliferation range. Therefore, an accurate and standardized Ki67 scoring is pivotal both in routine diagnostics and larger multicenter studies.Experimental Design: We validated a novel fully automated Ki67 scoring approach that relies on only minimal a priori knowledge on cell properties and requires no training data for calibration. We applied our approach to 1,082 breast cancer samples from the neoadjuvant GeparTrio trial and compared the performance of automated and manual Ki67 scoring.Results: The three groups of autoKi67 as defined by low (35%) automated scores showed pCR rates of 5.8%, 16.9%, and 29.5%, respectively. AutoKi67 was significantly linked to prognosis with overall and progression-free survival P values P-OS < 0.0001 and P-PFS < 0.0002, compared with P-OS < 0.0005 and P-PFS < 0.0001 for manual Ki67 scoring. Moreover, automated Ki67 scoring was an independent prognosticator in the multivariate analysis with P-OS = 0.002, P-PFS = 0.009 (autoKi67) versus P-OS = 0.007, P-PFS = 0.004 (manual Ki67).Conclusions: The computer-assisted Ki67 scoring approach presented here offers a standardized means of tumor cell proliferation assessment in breast cancer that correlated with clinical endpoints and is deployable in routine diagnostics. It may thus help to solve recently reported reliability concerns in Ki67 diagnostics. (C)2014 AACR.