Reduced expression of Raf-1 kinase inhibitory protein in renal cell carcinoma: A significant prognostic marker

Aims: 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. Methods: 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. Results: 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). Conclusion: Our results strongly suggested that reduced RKIP expression is associated with tumour progression and metastasis. Therefore,we concluded that RKIPexpression is a significant prognostic marker for patients with RCC.