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 RKIP expression is a significant prognostic marker for patients with RCC.