TGF-beta1 in patients with renal cell carcinoma

Up to now, clinical tumor-markers for renal cell carcinoma (RCC) have been lacking. Increased plasma levels of transforming growth factor-beta1 (TGF-beta1) were described as a tumor-marker and prognostic factor in RCC. The aim of this study was to test the clinical suitability of plasma TGF-beta1 as a tumor-marker for RCC. The concentrations of active and latent TGF-beta1 were determined in plasma of patients with localized (n = 39) and metastasised (n = 17) RCC. A newly developed, highly sensitive ELISA, which is specific for the isoform beta1, was used. Active TGF was directly measured in the EDTA plasma. To determine the amount of latent TGF-beta1, which is bound predominantly at beta2-macroglobulin, an optimized activation procedure was applied. Patients with localized RCC showed median concentrations of 16,700 ng/l (6,200-54,800 ng/l) for latent TGF-beta1. A total of 94 patients with various nonmalignant urological diseases were recruited as a control group. In comparison, this group had median concentrations of 19,900 ng/l (2,640-52,300 ng/l) for latent TGF-beta1. There was no significant difference (nonparametric Kruskal-Wallis ANOVA) between these groups. Patients with metastatic RCC showed median concentrations of 34,500 ng/l (6,800-48,960 ng/l) for latent TGF-beta1. In comparison to the localized RCC group, a statistically significant difference was found. Plasma levels after operative therapy (days 1, 5 and 10) and during follow-up without evidence of disease (2-6 months) showed no significant differences. Contrary to other study groups, our results suggest that TGF-beta1 is not a suitable tumor-marker for the diagnosis of localized RCC. In the face of higher TGF-beta1 plasma levels in metastatic disease, TGF-beta1 may be useful in the early detection of RCC recurrence or to control the success of immunochemotherapy.