EXPRESSION OF THE INTERLEUKIN-6 RECEPTOR IN PRIMARY RENAL-CELL CARCINOMA

Aims-Interleukin 6 (IL-6) is expressed in the majority of renal cell c arcinomas and has an important role in the proliferation of some renal cell carcinoma cell Lines. This action is mediated by two membrane pr oteins, gp80 (the IL-6 receptor; IL-6R), which binds IL-6, and gp130, which transduces the signal. The soluble form of gp80 (sIL-6R) is able to activate gp130 when complexed to the IL-6 molecule. These consider ations prompted an investigation of IL-GR expression in this malignanc y. IL-6, C reactive protein (CRP), and sIL-6R were also measured in se rum and correlated to clinical and pathological features. Methods-Immu nostaining was performed on cryostat sections from renal cell carcinom a tumours with M91, an anti-IL-6R monoclonal antibody, using the alkal ine phosphatase antialkaline phosphatase technique. The proliferation index was measured using the KI-67 monoclonal antibody. CRP, IL-6, and sIL-6R were measured in serum before nephrectomy, using an immunoenzy matic or immunoradiometric assay. Results-There were significant diffe rences in survival in patients with tumours larger than 8 cm, metastas is at diagnosis, high nuclear grade tumours, detectable serum concentr ations of IL-6 (correlated to CRP serum concentration), more than 4% p roliferating cells, and the presence of the IL-BR in situ. Furthermore , the serum IL-6 concentration correlated with tumour size and stage. The mean serum sIL-6R concentration was not significantly different fr om that observed in 40 normal subjects. Tumour IL-6R expression was pr esent in 10 samples. There was a significant association between the p resence of the IL-6 receptor in tumours and tumour stage, nuclear grad e, proliferation index, and serum IL-6. Conclusions-This study reveale d the importance of IL-6/CRP and IL-6R expression in situ as potential new prognostic factors and opens the way to new therapeutic strategie s in renal cell carcinoma.