Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, South Korea.
Pathology. 2012 Oct;44(6):534-9. doi: 10.1097/PAT.0b013e32835817e8.
Renal cell carcinoma (RCC) is the third most common urological malignancy. Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor and useful prognostic marker for a variety of human cancers. The aims of this study were to evaluate RKIP expression in RCC patients, and to determine the association of this protein with metastasis and its prognostic significance.
Immunohistochemical staining for RKIP was performed for 310 cases of various types of RCC. We investigated whether RKIP expression correlated with clinicopathological parameters and patient outcomes.
The tubules of normal kidney showed consistently strong cytoplasmic and membranous RKIP immunoreactivity. RKIP expression was significantly reduced in 42.2% of RCC cases (negative 24.5%, weakly positive 17.7%). Reduced RKIP expression was significantly related to presence of distant metastasis (p < 0.001), higher disease stage (p = 0.004), larger tumour size (p = 0.005), and sarcomatoid subtype (p = 0.001). Univariate analysis showed that reduced RKIP expression was significantly associated with poor overall survival and disease-free survival (p = 0.0014 and 0.0001, respectively). The multivariate analysis revealed that reduced RKIP expression was an independent predictor of poor prognosis for overall patient survival (p = 0.035).
Our results strongly suggested that reduced RKIP expression is associated with tumour progression and metastasis. Therefore, we concluded that RKIP expression is a significant prognostic marker for patients with RCC.
肾细胞癌（RCC）是第三大常见的泌尿系统恶性肿瘤。Raf-1 激酶抑制剂蛋白（RKIP）已成为多种人类癌症的重要转移抑制因子和有用的预后标志物。本研究旨在评估 RKIP 在 RCC 患者中的表达，并确定该蛋白与转移的相关性及其预后意义。
对 310 例不同类型的 RCC 进行了 RKIP 的免疫组织化学染色。我们研究了 RKIP 表达是否与临床病理参数和患者预后相关。
正常肾脏的肾小管显示出强烈的细胞质和膜性 RKIP 免疫反应性。在 42.2%的 RCC 病例中（阴性 24.5%，弱阳性 17.7%），RKIP 表达明显降低。RKIP 表达降低与远处转移（p<0.001）、较高的疾病分期（p=0.004）、更大的肿瘤大小（p=0.005）和肉瘤样亚型（p=0.001）显著相关。单因素分析显示，RKIP 表达降低与总生存和无病生存不良显著相关（p=0.0014 和 0.0001）。多因素分析显示，RKIP 表达降低是患者总生存不良的独立预测因子（p=0.035）。
我们的结果强烈表明，RKIP 表达降低与肿瘤进展和转移相关。因此，我们得出结论，RKIP 表达是 RCC 患者的一个重要预后标志物。
