Hida Akira I, Oshiro Yumi, Inoue Hiromichi, Kawaguchi Hidetoshi, Yamashita Natsumi, Moriya Takuya
Department of Pathology, Matsuyama Red Cross Hospital, 1 Bunkyo, Matsuyama, Ehime, 790-8524, Japan,
Breast Cancer. 2015 Mar;22(2):129-34. doi: 10.1007/s12282-013-0460-8. Epub 2013 Mar 31.
The Ki67 labeling index (LI) reflects the proliferative activity of breast cancers and defines luminal A and B tumors; however, no detailed method to measure Ki67 has been standardized. Here, we propose a fast and easy way to evaluate Ki67.
Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 (MIB-1) was performed on 235 primary invasive ductal carcinomas. For each sample, a hot spot with many Ki67+ cells was identified using a low-power field (40×, 4× objective). Three independent areas in high-power field (400×) were selected at the hot spot, and all cancer cells in the 3 areas were manually counted to calculate LI (% Ki67+ cells). Alternatively, micrographs taken at 100× and 200× fields including the hot spot were shown to 2 pathologists, who visually assessed percentages of Ki67+ cells in 10 % intervals at a glance (Eye-10).
Eye-10 and LI were strongly correlated (r = 0.9412, P < 0.0001). All cases of Eye-10 ≥ 30 % had LI > 14 %; most of those <10 % had LI < 14 %. Of 170 ER+/HER2- tumors, Eye-10-based subtypes matched 87 % of LI-driven subtypes, and interobserver agreement was good (κ = 0.705).
Eye-10 is far easier than counting many cancer cells and useful for classifying breast cancers. Eye-10 can exclude obviously high and low Ki67 cases, leaving a "gray zone" around a cutoff point. Combining Eye-10 and manual counting is a good candidate for a standard method to evaluate Ki67.
Ki67标记指数(LI)反映乳腺癌的增殖活性,并用于定义腔面A型和B型肿瘤;然而,尚未有测量Ki67的详细方法被标准化。在此,我们提出一种快速简便的评估Ki67的方法。
对235例原发性浸润性导管癌进行雌激素受体(ER)、孕激素受体(PgR)、HER2和Ki67(MIB-1)的免疫组化染色。对于每个样本,使用低倍视野(40×,4倍物镜)确定一个有许多Ki67阳性细胞的热点区域。在该热点区域的高倍视野(400×)中选择三个独立区域,手动计数这三个区域中的所有癌细胞以计算LI(Ki67阳性细胞百分比)。或者,将包括热点区域的100×和200×视野拍摄的显微照片展示给2名病理学家,他们一眼就能直观地以10%的间隔评估Ki67阳性细胞的百分比(Eye-10)。
Eye-10与LI密切相关(r = 0.9412,P < 0.0001)。所有Eye-10≥30%的病例LI>14%;大多数<10%的病例LI<14%。在170例ER+/HER2-肿瘤中,基于Eye-10的亚型与基于LI的亚型匹配率为87%,观察者间一致性良好(κ = 0.705)。
Eye-10比计数大量癌细胞要容易得多,并且对乳腺癌分类很有用。Eye-10可以排除明显高Ki67和低Ki67的病例,在一个临界点周围留下一个“灰色区域”。将Eye-10与手动计数相结合是评估Ki67的标准方法的一个良好候选方案。