Veronese S M, Maisano C, Scibilia J
Department of Pathology, Niguarda Hospital, Milano, Italy.
Anticancer Res. 1995 Nov-Dec;15(6B):2717-22.
Tumor proliferation index was evaluated in 246 samples of breast carcinoma using Ki-67 and MIB-1 monoclonal antibodies on frozen and paraffin sections, respectively, with the purpose to compare the two proliferation indices from both a quantitative and prognostic point of view.
All determinations were performed with the same immunohistochemical procedure (Avidin-Biotin Complexes). The prognostic relevance of tumor proliferation index, defined by both the antibodies, was investigated in 127 patients. Ki-67 and MIB-1 median values were used to obtain two groups of patients at different risk and life-table analysis (Mantel-Cox) was performed to assess the probabilities of overall survival (OS) and relapse-free survival (RFS). The median time of observation was 61 months.
Ki-67 and MIB-1 values were exponentially distributed with overlapping ranges varying from 2% to 90%. Ki-67 mean and median values were 16.7% and 14.0%, respectively, compared to 22.5% and 20% for MIB-1. Ki-67 and MIB-1 mean values were statistically different (t = -4.396; p < 0.001), while no difference was observed for MIB-1 mean values on frozen and paraffin sections (t = 1.35; p = n.s.). Ki-67 and MIB-1 values were statistically correlated (Spearman's coefficient = 0.75; p < 0.0001) and directly associated (agreement rate = 79.3%; p < 0.0001). Patients with tumors having a high proportion of MIB-1 positive cells showed a higher 5-year probability of relapse of disease (43.7% versus 27.6%; p = 0.02) and death (35.4% versus 15.8%; p = 0.007) than those with a low one. In parallels Ki-67 was found to be prognostically relevant for OS (32.2% versus 16.2%; p = 0.02) but not for RFS (40.7% versus 27.9%; p = 0.10).
Such results indicate that the detection of proliferative activity on paraffin sections with MIB-1 monoclonal antibody provides in formation analogous to or even better than that obtained with Ki-67 antibody on frozen ones. Moreover, it represents a valuable tool to obtain kinetic data on "routine" histological samples and, above all, to give prognostic evaluations on the clinical outcome of breast cancer patients.
分别使用Ki-67和MIB-1单克隆抗体在冰冻切片和石蜡切片上对246例乳腺癌样本的肿瘤增殖指数进行评估，目的是从定量和预后的角度比较这两种增殖指数。
所有测定均采用相同的免疫组织化学方法（抗生物素蛋白-生物素复合物法）。在127例患者中研究了由这两种抗体定义的肿瘤增殖指数的预后相关性。使用Ki-67和MIB-1的中位数来获得两组处于不同风险的患者，并进行生命表分析（Mantel-Cox法）以评估总生存期（OS）和无复发生存期（RFS）的概率。观察的中位时间为61个月。
Ki-67和MIB-1的值呈指数分布，重叠范围从2%到90%不等。Ki-67的平均值和中位数分别为16.7%和14.0%，而MIB-1的分别为22.5%和20%。Ki-67和MIB-1的平均值在统计学上有差异（t = -4.396；p < 0.001），而在冰冻切片和石蜡切片上MIB-1的平均值无差异（t = 1.35；p = 无统计学意义）。Ki-67和MIB-1的值在统计学上具有相关性（Spearman系数 = 0.75；p < 0.0001）且呈直接关联（一致率 = 79.3%；p < 0.0001）。MIB-1阳性细胞比例高的肿瘤患者疾病复发的5年概率（43.7%对27.6%；p = 0.02）和死亡概率（35.4%对15.8%；p = 0.007）高于比例低的患者。同时发现Ki-67对总生存期具有预后相关性（32.2%对16.2%；p = 0.02），但对无复发生存期无相关性（40.7%对27.9%；p = 0.10）。
这些结果表明，用MIB-1单克隆抗体在石蜡切片上检测增殖活性所提供的信息与用Ki-67抗体在冰冻切片上获得的信息相似甚至更好。此外，它是获取“常规”组织学样本动力学数据的有价值工具，最重要的是，可对乳腺癌患者的临床结局进行预后评估。
