Carlota Claussen1, Alma-Verena Rausch2, Susanne Lezius3, Ali Amirkhosravi4, Monica Davila4, John L Francis4, Yohei M Hisada5,6, Nigel Mackman5, Carsten Bokemeyer1, Barbara Schmalfeldt2, Sven Mahner7, Florian Langer8. 1. II. Medizinische Klinik und Poliklinik, Onkologisches Zentrum - Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. 2. Klinik und Poliklinik für Gynäkologie, Zentrum für Operative Medizin, Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. 3. Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. 4. Florida Hospital Center for Thrombosis Research, 2566 Lee Road, Winter Park, FL 32789, USA. 5. University of North Carolina at Chapel Hill, 111 Mason Farm Road, 2312B Medical Biomolecular Research Building, Campus Box #7126, Chapel Hill, NC 27599, USA. 6. K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway. 7. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München (LMU), Campus Großhadern und Innenstadt, Marchioninistr. 15, 81377 München, Germany. 8. II. Medizinische Klinik und Poliklinik, Onkologisches Zentrum - Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. Electronic address: langer@uke.de.
Abstract
BACKGROUND: Tissue factor (TF) is involved in tumor growth and metastasis and contributes to venous thromboembolism (VTE) in cancer, including gynecological malignancies. The diagnostic value of microvesicle-associated TF procoagulant activity (MV TF PCA) in women with suspected ovarian cancer, however, has not been studied. OBJECTIVE: To evaluate MV TF PCA as a diagnostic tool in women with an ovarian mass of unknown etiology and as a predictive biomarker for perioperative VTE. METHODS: Plasma MVs were isolated by high-speed centrifugation and analyzed for TF-specific PCA by single-stage clotting assay. In addition, plasma TF antigen and soluble P-selectin (sCD62P) were measured by ELISA. RESULTS: D-Dimer, MV TF PCA, and sCD62P, but not the tumor marker, CA-125, significantly differentiated patients with malignant (n=40) from those with benign tumors (n=15) and healthy controls (n=34). In cancer patients, only D-Dimer and CA-125 correlated with the FIGO stage. An abnormal D-dimer had the highest sensitivity for the diagnosis of cancer, while MV TF PCA above the ROC curve-derived cut-off value of 182U/mL had the highest specificity. By multivariate logistic regression analysis, addition of MV TF PCA conferred diagnostic benefit to the single variables, CA-125 (p=0.052) and D-dimer (p=0.019). Perioperative VTE occurred in 16% of cancer patients and was associated with an advanced FIGO stage, but not MV TF PCA. There was no difference in plasma TF antigen levels between study groups. CONCLUSIONS: MV TF PCA, but not plasma TF antigen, may provide valuable additional information for the diagnostic work-up of women with suspected ovarian cancer.
BACKGROUND:Tissue factor (TF) is involved in tumor growth and metastasis and contributes to venous thromboembolism (VTE) in cancer, including gynecological malignancies. The diagnostic value of microvesicle-associated TF procoagulant activity (MV TF PCA) in women with suspected ovarian cancer, however, has not been studied. OBJECTIVE: To evaluate MV TF PCA as a diagnostic tool in women with an ovarian mass of unknown etiology and as a predictive biomarker for perioperative VTE. METHODS: Plasma MVs were isolated by high-speed centrifugation and analyzed for TF-specific PCA by single-stage clotting assay. In addition, plasma TF antigen and soluble P-selectin (sCD62P) were measured by ELISA. RESULTS: D-Dimer, MV TF PCA, and sCD62P, but not the tumor marker, CA-125, significantly differentiated patients with malignant (n=40) from those with benign tumors (n=15) and healthy controls (n=34). In cancerpatients, only D-Dimer and CA-125 correlated with the FIGO stage. An abnormal D-dimer had the highest sensitivity for the diagnosis of cancer, while MV TF PCA above the ROC curve-derived cut-off value of 182U/mL had the highest specificity. By multivariate logistic regression analysis, addition of MV TF PCA conferred diagnostic benefit to the single variables, CA-125 (p=0.052) and D-dimer (p=0.019). Perioperative VTE occurred in 16% of cancerpatients and was associated with an advanced FIGO stage, but not MV TF PCA. There was no difference in plasma TF antigen levels between study groups. CONCLUSIONS: MV TF PCA, but not plasma TF antigen, may provide valuable additional information for the diagnostic work-up of women with suspected ovarian cancer.