Clinical Significance of Circulation Tissue Factor (TF) in Women with Suspected Ovarian Cancer

Abstract

Background: The interplay between malignancy, inflammation, and coagulation is well established. It is currently unclear, however, whether preoperative assessment of circulating TF provides valuable additional information in women presenting with ovarian masses of unknown etiology. Aims: To evaluate circulating TF as a diagnostic tool in suspected ovarian cancer. Methods: In a prospective single-center cohort study, we measured preoperative plasma levels of D-dimer, TF antigen, microparticle-associated TF-specific procoagulant activity (MP TF PCA), and soluble P-selectin (sCD62P) in 40 women with a final diagnosis of ovarian cancer in comparison to 15 women with benign tumors, all of whom underwent exploratory surgery, and 34 healthy females. Results: D-Dimer, MP TF PCA, and sCD62P, but not TF antigen and CA125, were significantly increased in cancer patients, while levels of hemostatic markers were similar in patients with benign tumors and healthy controls. Plasma depletion of MPs did not significantly alter TF antigen levels, as measured by ELISA, suggesting that this assay predominantly captured a soluble TF variant. In cancer patients, only D-Dimer and CA125 correlated with the FIGO stage. Abnormal levels of D-dimer had the highest sensitivity (93%), while increased MP TF PCA had the highest specificity (78%) for the diagnosis of cancer. Perioperative venous thromboembolism (VTE) occurred in 16% of cancer patients and was associated with an advanced FIGO stage, while sCD62P and plasma fibrinogen, an acute-phase reactant, were correlated with the Khorana score, a validated VTE risk assessment tool in ambulatory cancer patients. Conclusion: While D-dimer, by reflecting the overall impact of the cancer on the hemostatic system, is correlated with tumor burden, shedding of MP TF PCA may provide complementary information relevant to malignant transformation and cancer biology. In this regard, technically demanding analysis of MP TF PCA cannot be replaced by measurement of plasma TF antigen.