Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
BJU Int. 2014 Apr;113(4):668-73. doi: 10.1111/bju.12263. Epub 2013 Aug 13.
To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear-cell renal cell carcinoma (ccRCC).
Immunohistochemistry for Ki67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for clinically localized (M0) ccRCC and Ki67 expression >10% was considered abnormal. Clinical and pathological data elements were entered into an institutional review board-approved database. The Kaplan-Meier method and Cox regression models were used to analyse disease-free survival (DFS) and cancer-specific survival (CSS) probabilities.
Of 401 patients, 59.6% were males. The median (range) age was 58 (17-85) years, follow-up was 22 (0-150) months and time to death was 27 (0-150) months. A total of 20.2% of patients had advanced stage (pT3-T4) and 31% had advanced grade (3-4) disease. Abnormal expression of Ki67 was seen in 6.5% of our cohort and was associated with adverse pathological features (P < 0.05). Patients with high expression of Ki67 were found to have 5-year DFS and CSS rates of 67 and 84%, respectively, vs 87 and 95%, respectively, in those with normal expression (P < 0.001 and P < 0.05, respectively). In multivariable analyses, adjusting for stage and grade, abnormal Ki67 expression was an independent predictor of DFS (hazard ratio [HR] 3.77, P = 0.011, 95% confidence interval [CI] 1.35-10.52), but not of CSS (HR 3.51 P = 0.137, 95% CI 0.671-18.35).
Our findings support the role of Ki67 as a powerful independent predictor of inferior oncological outcomes in patients with ccRCC. Further prospective studies are needed to determine the clinical applicability of these findings.
验证 Ki67 表达对接受局部治疗的临床局限性透明细胞肾细胞癌（ccRCC）患者肿瘤学结局的影响。
对接受根治性或部分肾切除术治疗的临床局限性（M0）ccRCC 患者的组织微阵列进行 Ki67 免疫组织化学染色，Ki67 表达>10%被认为是异常的。临床和病理数据元素被输入到机构审查委员会批准的数据库中。使用 Kaplan-Meier 方法和 Cox 回归模型分析无病生存率（DFS）和癌症特异性生存率（CSS）概率。
在 401 名患者中，59.6%为男性。中位（范围）年龄为 58（17-85）岁，随访时间为 22（0-150）个月，死亡时间为 27（0-150）个月。20.2%的患者有晚期（pT3-T4）分期，31%有晚期（3-4）分级。我们的队列中有 6.5%的患者出现 Ki67 异常表达，与不良病理特征相关（P<0.05）。Ki67 高表达患者的 5 年 DFS 和 CSS 率分别为 67%和 84%，而 Ki67 正常表达患者的 5 年 DFS 和 CSS 率分别为 87%和 95%（P<0.001 和 P<0.05）。在多变量分析中，调整分期和分级后，异常 Ki67 表达是 DFS 的独立预测因子（风险比[HR]3.77，P=0.011，95%置信区间[CI]1.35-10.52），但不是 CSS（HR 3.51，P=0.137，95%CI 0.671-18.35）。
我们的研究结果支持 Ki67 作为预测 ccRCC 患者肿瘤学结局不良的有力独立预测因子的作用。需要进一步的前瞻性研究来确定这些发现的临床适用性。
