Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

Background: Interferon-alpha (IFN-alpha) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-alpha receptor ( IFNAR). We investigated the role of IFNAR in RCC. Methods: We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT- PCR), and IFNAR2 protein using Western blotting. Results: The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N) for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/ N ratio of IFNAR2 correlated with poor differentiation (P < 0.05), local invasion (P < 0.001), and metastasis (P < 0.0001). By multivariate analysis, a high T/N ratio of IFNAR2 predicted a shortened overall survival in all cases (P < 0.05) and a shorter disease-free survival in those without metastasis (M0; 68 cases, P < 0.05). Impressively, patients with a poorer response to IFNa treatment had a higher IFNAR2 T/N ratio than those who had a good response ( P < 0.05). IFNAR2c protein expression was higher in the primary tumors in patients with metastases ( M1; 35 cases) compared to those without ( P < 0.0001). Conclusion: IFNAR2 is associated with the progression of RCC.