Prognostic significance of vitamin D receptor and retinoid X receptor expression in renal cell carcinoma

Purpose: The active form of vitamin D3, that is l alpha,25-dihydroxyvitamin D3, binds with vitamin D receptor, which forms a complex with retinoid X receptors a, 0 and gamma to manifest antitumor effects. We examined the expression of vitamin D receptor and retinoid X receptors in renal cell carcinoma and elucidated the prognostic significance of these receptors. Materials and Methods: We performed immunohistochemical examination of vitamin D receptor, and retinoid X receptors alpha, beta and gamma in nephrectomized specimens of 68 patients with renal cell carcinoma. We analyzed the correlation between the expression of these receptors and clinicopathological parameters or patient survival. Mean followup was 68.2 months. Results: No significant correlation was found between the expression of vitamin D receptor, retinoid X receptor a or 0 and clinicopathological parameters. In contrast, retinoid X receptor gamma expression correlated significantly with tumor stage (p = 0.009) and distant metastasis (p = 0.005). The 5-year cancer specific survival rate was higher in patients with retinoid X receptor gamma positive renal cell carcinoma than those with retinoid X receptor gamma negative renal cell carcinoma (79.3% vs 40.0%, p < 0.05). Cox regression analysis revealed that retinoid X receptor gamma expression, tumor status and lymph node status were significant independent prognostic factors in patients with renal cell carcinoma (p < 0.05). A significant correlation was observed between the expression of retinoid X receptor gamma and tumor stage, distant metastasis or the 5-year cancer specific survival rate. Furthermore, retinoid X receptor gamma expression was an independent prognostic factor in patients with renal cell carcinoma. Conclusions: Our observations suggest that alterations of vitamin D receptor and retinoid X receptor expression may be involved in renal carcinogenesis and retinoid X receptor gamma expression may be a useful prognostic marker in patients with renal cell carcinoma.