Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, Japan.
Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
Breast Cancer. 2018 Nov;25(6):768-777. doi: 10.1007/s12282-018-0885-1. Epub 2018 Jun 29.
Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown.
We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist's scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test.
Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist's scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031).
The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.
由于重复性差，常规分析 Ki-67 不被广泛推荐用于临床决策。此外，对病理学家来说，计数大量细胞可能很费力。最近开发了用于免疫组织化学分析的数字图像分析；然而，使用图像分析获得的 Ki-67 指数的临床疗效尚不清楚。
我们使用日本东海大学的病理学数据库，回顾性地确定了具有免疫组织化学 Ki-67 和生存数据的女性乳腺癌患者。由三位病理学家对 Ki-67 表达进行评分。对切片进行扫描并转换为虚拟切片；使用图像分析计数 Ki-67 阳性细胞。通过 2×2 分析评估病理学家评分和图像分析获得的 Ki-67 指数。使用 Kaplan-Meier 方法评估 Ki-67 指数与生存结果之间的关系，并使用对数秩检验进行比较。
基于 2×2 分析，所有患者的图像分析获得的 Ki-67 指数与病理学家评分中度相关（κ 0.41；敏感性，0.573；特异性，0.878）。对于激素受体阳性、人表皮生长因子受体 2 阴性和 I 期或 II 期患者，高 Ki-67 指数与低 Ki-67 指数相比，与复发无进展生存期较差相关，这些患者是由病理学家评分（p<0.001）和使用图像分析（p=0.031）获得的。
图像分析获得的 Ki-67 指数与病理学家评分中度相关。数字图像分析可有效测量 Ki-67 值，因为它们与激素受体阳性、人表皮生长因子受体 2 阴性和 I 期或 II 期患者的无复发生存期相关。
