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Background  Interferon-α (IFN-α) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-α 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 IFN-α 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.

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