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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. Purpose: 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 (macro-phage-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. Implications: 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. [J Natl Cancer Inst 85:1225-1230, 1993]

The progression of a tumor is a complex process involving many different components. In the case of small cell carcinoma of the lung (SCCL), progression seems to involve the coagulation of blood. Fibrin, the clot material, may surround the tumor and form a favorable matrix for the development of new blood vessels which help feed the growing tumor. The administration of anticoagulants to patients with SCCL prolongs survival and increases tumor regression, but the mechanisms behind this phenomenon are not clear. Also uncertain are the reasons for the activation of the clotting mechanisms, and the reasons why normal mechanisms do not work to dissolve the tumor-associated clot. In order to provide more data about the mechanisms at work, histological staining was performed on autopsy specimens from six patients with SCCL. Specific immunological stains were used to localize within the tumor various components of the blood coagulation process. Tissue factor, a protein which is capable of activating coagulation, was present within some, but not all, of the tumor cells. Fibrin, the fibrous protein resulting from the coagulation process, was found at the border between the tumor and the host tissue. This indicates that the enzyme thrombin had acted upon the fibrinogen within the tumor tissue, but the mechanism of thrombin formation was not apparent. In addition, urokinase and tissue plasminogen activator, which are responsible for dissolving clots under normal conditions, were found around the blood vessels, but not in the tumor itself. These data suggest that the coagulation is probably controlled by the tumor cells themselves, and indicate why the anticoagulant warfarin has beneficial effects on patients with SCCL. But since the inhibition of the clot-forming thrombin by warfarin is not complete, it may be possible to improve treatment by using other factors which reduce coagulation, such as tissue plasminogen activator. (Consumer Summary produced by Reliance Medical Information, Inc.)