title: Plasma tissue factor antigen in localized prostate cancer: distribution, clinical significance and correlation with haemostatic activation markers.
abstract: Tissue factor (TF) is involved in cancer growth and metastasis, and haemostatic abnormalities are found in most patients with advanced malignancies, including prostate cancer (PC). Because anti-haemostatic agents are increasingly screened for their potential to prolong survival in tumor patients, a detailed characterization of haemostatic markers in selected cancer subtypes and clinical stages is warranted. In this study, we measured preoperative plasma TF antigen in a large cohort of patients with localized PC and correlated its levels with markers of coagulation and platelet activation, prostate-specific antigen (PSA), and histopathological findings to explore its potential as a prognostic marker in this tumor entity. Out of 140 patients, 19% and 23% had plasma TF antigen levels of <40 pg/ml (low-TF) and >200 pg/ml (high-TF), respectively, which was substantially higher than in 42 healthy male controls. Patients also had low-grade systemic coagulation activation as evidenced by elevated D-dimer, F1 + 2, and PAP plasma levels. Furthermore, similar to sP-selectin and sCD40L antigen, flow cytometric analysis of platelet-derived microparticles in plasma revealed significantly increased numbers in high-TF as compared to low-TF patients and controls. Whereas elevated D-dimer was associated with larger and less differentiated tumors, preoperative plasma TF antigen levels (median [IQR]) were higher in patients with (161 pg/ml [100-236]) than in those without recurrent PC (105 pg/ml [52-182]), as indicated by a serum PSA of >0.1 ng/ml during ambulatory follow-up. In patients with localized PC, preoperative plasma TF antigen levels correlate with platelet activation in vivo and may indicate an increased risk for recurrent disease.
authors.affiliation: II. Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Hamburg, Germany. langer@uke.uni-hamburg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Langer
authors.forename: Felix Kyoung-Hwan
authors.initials: FK
authors.lastname: Chun
authors.forename: Ali
authors.initials: A
authors.lastname: Amirkhosravi
authors.forename: Martin
authors.initials: M
authors.lastname: Friedrich
authors.forename: Sven
authors.initials: S
authors.lastname: Leuenroth
authors.forename: Barbara
authors.initials: B
authors.lastname: Eifrig
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: John L
authors.initials: JL
authors.lastname: Francis
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001777:Blood Coagulation; D023201:CD40 Ligand / Q000097:blood; D002454:Cell Differentiation; D004211:Disseminated Intravascular Coagulation / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D015539:Platelet Activation; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D011516:Prothrombin; D012008:Recurrence; D018570:Risk Assessment; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; D010446:Peptide Fragments; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D023201:CD40 Ligand; D011516:Prothrombin; D013925:Thromboplastin; D005341:Fibrinolysin; D017430:Prostate-Specific Antigen