Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, China.
Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Urology. 2015 Feb;85(2):483.e9-483.e14. doi: 10.1016/j.urology.2014.10.022. Epub 2015 Jan 2.
To evaluate the prognostic significance of Notch1 activation in patients with clear-cell renal cell carcinoma (ccRCC).
We retrospectively enrolled 203 patients with ccRCC undergoing nephrectomy at Zhongshan Hospital of Fudan University between 2003 and 2004. Notch1 activation was assessed by immunohistochemical staining of the intracellular domain of Notch1 (ICN1) in specimens of patients. The Kaplan-Meier method, Cox regression models, and Harrell concordance index (C-index) calculation were used to evaluate the prognostic value of ICN1 expression and its association with clinicopathologic features.
Tumor tissues from patients with advanced TNM stage and Fuhrman grade exhibited elevated ICN1 expression, which correlated positively with tumor size, Fuhrman grade, and tumor necrosis. Moreover, high ICN1 expression indicated poor overall survival and recurrence-free survival of patients with ccRCC. After backward elimination, ICN1 expression, as well as Fuhrman grade, Eastern Cooperative Oncology Group performance status, and TNM stage, was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of well-established TNM, University of California Integrated Staging System, and Mayo Clinic stage, size, grade, and necrosis prognostic models was improved when ICN1 expression was added. Furthermore, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 5 years after surgery.
Notch1 activation is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.
评估 Notch1 激活在肾透明细胞癌（ccRCC）患者中的预后意义。
我们回顾性纳入了 203 例 2003 年至 2004 年在复旦大学中山医院接受肾切除术的 ccRCC 患者。通过 Notch1 细胞内结构域（ICN1）的免疫组织化学染色评估患者标本中的 Notch1 激活情况。采用 Kaplan-Meier 方法、Cox 回归模型和 Harrell 一致性指数（C-index）计算来评估 ICN1 表达的预后价值及其与临床病理特征的相关性。
晚期 TNM 分期和 Fuhrman 分级的肿瘤组织表现出升高的 ICN1 表达，与肿瘤大小、Fuhrman 分级和肿瘤坏死呈正相关。此外，高 ICN1 表达提示 ccRCC 患者的总生存和无复发生存较差。经过向后消除，ICN1 表达以及 Fuhrman 分级、东部肿瘤协作组体能状态和 TNM 分期被确定为生存和复发的独立不良预后因素。加入 ICN1 表达后，既定的 TNM、加利福尼亚大学综合分期系统和 Mayo 诊所分期、大小、分级和坏死预后模型的预测准确性得到提高。此外，使用确定的独立预后因素生成了一个预测列线图，以评估术后 5 年患者的生存情况。
Notch1 激活是肾切除术后 ccRCC 患者复发和生存的潜在独立不良预后生物标志物。
