Plasma tissue factor antigen in localized prostate cancer: distribution, clinical significance and correlation with haemostatic activation markers.
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.
Langer
Florian
F
II. Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Hamburg, Germany. langer@uke.uni-hamburg.de
Chun
Felix Kyoung-Hwan
FK
Amirkhosravi
Ali
A
Friedrich
Martin
M
Leuenroth
Sven
S
Eifrig
Barbara
B
Bokemeyer
Carsten
C
Francis
John L
JL
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
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