Soluble Fas in serum from patients with renal cell carcinoma

Objectives. Fas/APO-1 is an apoptosis-signaling cell-surface receptor belon ging to the tumor necrosis factor receptor family. The Fas-Fas ligand syste m plays an important role in cytotoxic T-lymphocyte-mediated or natural kil ler cell-mediated cytotoxicity against tumor cells. Soluble Fas (sFas), gen erated by alternative splicing, has been reported to antagonize the interac tion of cell-surface Fas with Fas ligand. This study examined the level of sFas in the serum of patients with renal cell carcinoma (RCC) and investiga ted the correlation between the sFas level and clinicopathologic parameters of RCC. Methods. Using reverse transcriptase-polymerase chain reaction, we examined the production of sFas messenger RNA (mRNA) from the cultured human RCC ce ll lines ACHN and OUR-10 and from surgical specimens. We also measured sFas levels in the serum of 31 patients with RCC before and after nephrectomy u sing an sFas-specific enzyme-linked immunosorbent assay. Results. mRNA of sFas was identified both in cultured ACHN cells and human RCC tissues, although mRNA of wild-type Fas was exclusively predominant. Th e level of sFas in the serum of patients with RCC was significantly higher than that of normal controls, but sFas was not detectable in the supernatan t of cultured renal cancer cells. Preoperative and postoperative serum sFas levels did not clearly correlate with the patients' age or sex or with his tologic stage, grade, or cell type of RCC. The serum sFas level in patients with RCC correlated with tumor size. In 24 of the 31 cases, radical nephre ctomy reduced the serum sFas level within 3 months. Conclusions. Our results suggest that the elevated serum sFas level in pati ents with RCC might not be derived from the tumor itself but might reflect an immune response to the tumor burden. Serum sFas may be a useful indicato r of tumor burden in patients with RCC. (C) 2000, Elsevier Science Inc.