ARTICLE INFO ______________________________________________________________ ______________________Purpose: Increased expression of tissue factor (TF), a primary initiator of the extrinsic coagulation pathway, has been associated with a worse prognosis in a variety of solid tumors. We report for the first time the correlation of the immunohistochemical expression of tissue factor with clinical and pathological outcomes in clear cell carcinomas of the kidney. Materials and Methods: immunohistochemical expression of tissue factor was evaluated in 58 paraffin-embedded samples of clear cell carcinomas of the kidney treated at the same university hospital, that was correlated with clinical and pathological variables and with overall survival. Results: high intensity tissue factor expression (TF area > 10µm 2 ) was observed in 22.4% of the tumors (13 patients), and was an important predictor of overall mortality, both in univariate and multivariate analysis (p < 0.05). Median overall survival for both groups was 66 months; 78.2 months for patients in the group of lower TF expression and 27.5 months for patients in the group of higher TF expression (log rank p < 0.001). The hazard ratio for mortality was 9.7 (CI 3.7-25.6) for tumors with increased TF expression. Conclusions: Increased immunohistochemical expression of TF was an important independent predictor of mortality in a contemporary cohort of patients with clear cell carcinoma of the kidney. Further studies are necessary to define the role of TF in clinical practice.

Purposeto determine the usefulness of serum TF as a potential marker for patients with clear cell RCC.Materials and Methodsprospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®).ResultsMean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037).ConclusionsWe have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings.