Department of Diagnostic and Interventional Radiology, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel, 18-20 1090, Vienna, Austria.
Breast Cancer Res. 2018 Jun 19;20(1):58. doi: 10.1186/s13058-018-0991-1.
Numerous studies have analyzed associations between apparent diffusion coefficient (ADC) and histopathological features such as Ki-67 proliferation index in breast cancer (BC), with mixed results. The purpose of this study was to perform a multicenter analysis to determine relationships between ADC and expression of Ki-67 and tumor grade in BC.
For this study, data from six centers were acquired. The sample comprises 870 patients (all female; mean age, 52.6 ± 10.8 years). In every case, breast magnetic resonance imaging with diffusion-weighted imaging was performed. The comparison of ADC values in groups was performed by Mann-Whitney U test where the p values are adjusted for multiple testing (Bonferroni correction). The association between ADC and Ki-67 values was calculated by Spearman's rank correlation coefficient. Sensitivity, specificity, negative and positive predictive values, accuracy, and AUC were calculated for the diagnostic procedures. ADC thresholds were chosen to maximize the Youden index.
Overall, data of 870 patients were acquired for this study. The mean ADC value of the tumors was 0.98 ± 0.22 × 10 mm s. ROC analysis showed that it is impossible to differentiate high/moderate grade tumors from grade 1 lesions using ADC values. Youden index identified a threshold ADC value of 1.03 with a sensitivity of 56.2% and specificity of 67.9%. The positive predictive value was 18.2%, and the negative predictive value was 92.4%. The level of the Ki-67 proliferation index was available for 845 patients. The mean value was 12.33 ± 21.77%. ADC correlated with weak statistical significant with expression of Ki-67 (p = - 0.202, p < 0.001). ROC analysis was performed to distinguish tumors with high proliferative potential from tumors with low expression of Ki-67 using ADC values. Youden index identified a threshold ADC value of 0.91 (sensitivity 64%, specificity 50%, positive predictive value 67.7%, negative predictive value 45.0%).
ADC cannot be used as a surrogate marker for proliferation activity and/or for tumor grade in breast cancer.
许多研究分析了表观扩散系数（ADC）与乳腺癌（BC）中 Ki-67 增殖指数等组织病理学特征之间的关联，结果不一。本研究的目的是进行多中心分析，以确定 ADC 与 BC 中 Ki-67 表达和肿瘤分级之间的关系。
本研究获取了来自六个中心的数据。样本包括 870 名患者（均为女性；平均年龄 52.6±10.8 岁）。在每例患者中，均进行了乳腺磁共振成像加弥散加权成像。通过曼-惠特尼 U 检验比较组间 ADC 值，其中 p 值经多重检验（Bonferroni 校正）调整。通过 Spearman 秩相关系数计算 ADC 与 Ki-67 值之间的相关性。计算诊断程序的敏感性、特异性、阴性和阳性预测值、准确性和 AUC。选择 ADC 阈值以最大化 Youden 指数。
总体而言，本研究共获得 870 名患者的数据。肿瘤的平均 ADC 值为 0.98±0.22×10 mm/s。ROC 分析显示，使用 ADC 值无法区分高/中级别肿瘤与 1 级病变。Youden 指数确定了 ADC 值为 1.03 的阈值，其敏感性为 56.2%，特异性为 67.9%。阳性预测值为 18.2%，阴性预测值为 92.4%。Ki-67 增殖指数水平可用于 845 名患者。平均值为 12.33±21.77%。ADC 与 Ki-67 表达呈弱统计学显著相关（p=-0.202，p<0.001）。使用 ADC 值进行 ROC 分析，以区分具有高增殖潜能的肿瘤与 Ki-67 低表达的肿瘤。Youden 指数确定了 ADC 值为 0.91 的阈值（敏感性 64%，特异性 50%，阳性预测值 67.7%，阴性预测值 45.0%）。
ADC 不能用作乳腺癌增殖活性和/或肿瘤分级的替代标志物。
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