title: Tumor cell procoagulant and urokinase expression in carcinoma of the ovary.
abstract: BACKGROUND
  An association between cancer and increased blood coagulation has been observed for many years. Generally, there is an equilibrium between the coagulation system (fibrin deposition) and the fibrinolytic system (degradation of fibrin by enzymes). However, in malignant disease such as ovarian carcinoma, this equilibrium is disrupted, resulting in the abnormal activation of coagulation or hypercoagulability. Also, evidence indicates that various components of these pathways may contribute to the disorderly characteristics of malignancy, such as proliferation, invasion, and metastasis.
  
  
  OBJECTIVE
  Our purpose was to define the mode of interaction of tumor cells in ovarian carcinoma with both the coagulation (procoagulant-initiated) and fibrinolysis (urokinase-type plasminogen activator-initiated) (u-PA) pathways.
  
  
  METHODS
  Studies were performed on acetone-methylbenzoate-xylene-fixed tissue prepared from fresh resected primary tumor specimens from 15 patients with cystic epithelial ovarian carcinoma. None of the patients had received prior treatment. Antibodies were tested on control and tumor tissues in concentrations that provided maximum staining intensity with minimum background staining. Laboratory immunohistochemical techniques used purified, monospecific antibodies to detect coagulant antigens. Tests were performed utilizing antibodies to recombinant human tissue factor; factor VII; factor X; factor XIIIA; high-molecular-weight and low-molecular-weight forms of u-PA; tissue-type plasminogen activator; plasminogen; and the plasminogen activator inhibitors 1, 2, and 3. Monoclonal antibodies used for specific antigen detection included 1-8C6 (fibrinogen), T2G1 (fibrin), and EBM-11 (macrophage-specific).
  
  
  RESULTS
  The ovarian tumor cells expressed urokinase-type plasminogen activator in a pattern that was variable in intensity and distribution. Tumor cell plasminogen was not detected. Tumor cells also expressed tissue factor and coagulation pathway intermediates that resulted in local thrombin generation as evidenced by the conversion of fibrinogen (present in tumor connective tissue) to fibrin that was found to hug the surfaces of tumor nodules and individual tumor cells. Detected fibrin could not be accounted for on the basis of necrosis or a local inflammatory cell infiltrate.
  
  
  CONCLUSIONS
  These results are consistent with the existence of a dominant tumor cell-associated procoagulant pathway that leads to thrombin generation and hypercoagulability in carcinoma of the ovary.
  
  
  CONCLUSIONS
  In ovarian carcinoma the procoagulant pathway may contribute to tumor progression. Clinical trials of therapeutic drugs capable of limiting local coagulability (anticoagulants, protease inhibitors) are indicated in this tumor type.
authors.affiliation: Department of Veterans Affairs Medical and Regional Office Center, White River Junction, Vt.
authors.forename: L R
authors.initials: LR
authors.lastname: Zacharski
authors.forename: V A
authors.initials: VA
authors.lastname: Memoli
authors.forename: D L
authors.initials: DL
authors.lastname: Ornstein
authors.forename: S M
authors.initials: SM
authors.lastname: Rousseau
authors.forename: W
authors.initials: W
authors.lastname: Kisiel
authors.forename: B J
authors.initials: BJ
authors.lastname: Kudryk
mesh_terms: D001779:Blood Coagulation Factors / Q000032:analysis*; D002277:Carcinoma / Q000378:metabolism*; D003536:Cystadenocarcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D001779:Blood Coagulation Factors; D014568:Urokinase-Type Plasminogen Activator