Delahunt B, Bethwaite P B, Thornton A, Ribas J L
Department of Pathology, Wellington School of Medicine, University of Otago, New Zealand.
Cancer. 1995 Jun 1;75(11):2714-9. doi: 10.1002/1097-0142(19950601)75:11<2714::aid-cncr2820751113>3.0.co;2-x.
Although tumor staging is an important prognostic parameter for renal cell carcinoma (RCC), postnephrectomy survival interval is often difficult to predict for individual patients. This is the result of varied growth characteristics, which in tumors of similar stage govern both time to recurrence and rate of tumor dissemination. Polyclonal Ki-67 antibody labels a proliferation-specific antigen expressed in actively proliferating cells and is applicable to formalin fixed paraffin embedded archival tissue. This study was designed to test the prognostic utility of Ki-67 antigen labeling in a series of RCC and to compare the data with those derived from other markers of cell proliferation.
Polyclonal Ki-67 antibody staining of 206 cases of RCC was undertaken using the streptavidin-biotin method. Cases were grouped according to Ki-67 indices and Kaplan-Meier survival curves were constructed. Groups were compared in terms of survival for all cases and for each of Robson's stages using the log rank test. Further sections were stained for proliferating cell nuclear antigen (PCNA) and silver-staining nucleolar organizer regions (AgNORs). The prognostic significance of Ki-67 antigen, PCNA and AgNOR staining, histologic grade, and tumor stage were compared using Cox's proportional hazard model.
Ki-67 immunostaining was achieved for 173 cases with indices ranging from 0.1% to 30.4%. Division of tumors with indices 6% or less and greater than 6% showed a significant difference in survival between groups for all cases and for each Robson stage. Ki-67 and PCNA indices, AgNOR scores, and tumor dissemination (Robson Stage 3 and 4) retained a significant association with survival on multivariate analysis.
Polyclonal Ki-67 antibody immunostaining provides significant survival information that complements that derived by other markers of cell proliferation and tumor staging.
尽管肿瘤分期是肾细胞癌（RCC）重要的预后参数，但对于个体患者而言，肾切除术后的生存间隔往往难以预测。这是肿瘤生长特征各异所致，在相似分期的肿瘤中，这些特征决定了复发时间和肿瘤播散速率。多克隆Ki-67抗体可标记在活跃增殖细胞中表达的增殖特异性抗原，适用于福尔马林固定石蜡包埋的存档组织。本研究旨在检测Ki-67抗原标记在一系列肾细胞癌中的预后效用，并将数据与其他细胞增殖标志物的数据进行比较。
采用链霉亲和素-生物素法对206例肾细胞癌进行多克隆Ki-67抗体染色。根据Ki-67指数对病例进行分组，并构建Kaplan-Meier生存曲线。使用对数秩检验比较所有病例以及Robson各分期病例组的生存率。对进一步的切片进行增殖细胞核抗原（PCNA）染色和银染核仁组织区（AgNORs）染色。使用Cox比例风险模型比较Ki-67抗原、PCNA和AgNOR染色、组织学分级以及肿瘤分期的预后意义。
173例实现了Ki-67免疫染色，指数范围为0.1%至30.4%。将指数为6%及以下和大于6%的肿瘤进行划分，结果显示所有病例组以及Robson各分期组之间的生存率存在显著差异。在多变量分析中，Ki-67和PCNA指数、AgNOR评分以及肿瘤播散（Robson 3期和4期）与生存率仍存在显著关联。
多克隆Ki-67抗体免疫染色可提供重要的生存信息，对其他细胞增殖标志物和肿瘤分期所提供的信息起到补充作用。
