Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases

Abstract Tissue Factor Pathway Inhibitor (TFPI) prevents further participation of Tissue Factor (TF) in the coagulation process by forming a stable quaternary complex of TF-FVIIa-FXa-TFPI. Recently, plasma TFPI level were found to be elevated in patients with malignant disease outside the brain. Therefore the aim of this study was to investigate the TFPI plasma level in patients with primary brain tumors and intracerebral metastases. From May 2000 to December 2001 the total tissue factor pathway inhibitor antigen (TFPI) was preoperatively determined in blood samples of 225 patients with primary or metastatic brain tumors. Tumor histology classified as benign (WHO grade I and II) and malignant (WHO grade III and IV, intracerebral metastases) was correlated to plasma TFPI-levels. Plasma TFPI was significantly higher in patients with malignant tumors including intracerebral metastasis compared to benign tumors (80.1 ± 34.31 versus 64.3 ± 25.8 ng ml-1 [p < 0.01; t-test]). To exclude the influence of primary systemic neoplasms with secondary brain metastasis on plasma TFPI-level a subgroup of patients with primary brain tumors (meningioma, astrocytoma, oligodendroglioma and glioblastoma) was separated. In this group TFPI-level was also significantly elevated in patients with malignant (n = 66) (78.6 ± 29.9) compared to benign brain tumors (n = 127) (64.3 ± 25.8 ng ml-1 [p < 0.01; t-test]). To the authors' knowledge this is the first study describing the correlation of increased plasma TFPI and malignancy in patient with brain tumors. Further studies are needed to clarify the pathogenic mechanism and the clinical relevance of this phenomenon.

[1]  L. Rao,et al.  Tissue factor as a tumor procoagulant , 1992, Cancer and Metastasis Reviews.

[2]  E. Arbit,et al.  Hemostatic changes in patients with brain tumors , 2005, Journal of Neuro-Oncology.

[3]  R. Sawaya,et al.  Postoperative venous thromboembolism and brain tumors: part III. Biochemical profile , 2004, Journal of Neuro-Oncology.

[4]  B. Su,et al.  Quantitative reverse transcription-PCR measurement of tissue factor mRNA in glioma , 2002, Molecular biotechnology.

[5]  A. Lindahl,et al.  Elevated plasma levels of the factor Xa-TFPI complex in cancer patients. , 2002, Thrombosis research.

[6]  J. Birktoft,et al.  Structure and Biology of Tissue Factor Pathway Inhibitor , 2001, Thrombosis and Haemostasis.

[7]  P. Mannucci,et al.  Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis , 2001, British journal of haematology.

[8]  Y. Miyagi,et al.  Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor. , 1999, The Journal of clinical investigation.

[9]  A. Lindahl,et al.  Elevated TFPI in malignant disease: relation to cancer type and hypercoagulation , 1998, British journal of haematology.

[10]  J. Kuratsu,et al.  Expression of tissue factor in glioma. , 1996, Noshuyo byori = Brain tumor pathology.

[11]  P. Carmeliet,et al.  Role of tissue factor in embryonic blood vessel development , 1996, Nature.

[12]  J. Kuratsu,et al.  Expression of tissue factor correlates with grade of malignancy in human glioma , 1996, Cancer.

[13]  S. Tebbutt,et al.  Extrinsic-pathway activation in cancer with high factor Vlla and tissue factor , 1995, The Lancet.

[14]  W. Konigsberg,et al.  Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Osterud,et al.  Sites of Tissue Factor Pathway Inhibitor (TFPI) and Tissue Factor Expression under Physiologic and Pathologic Conditions , 1995, Thrombosis and Haemostasis.

[16]  D. Gomez,et al.  Partial characterization of novel serine proteinase inhibitors from human umbilical vein endothelial cells. , 1995, Archives of biochemistry and biophysics.

[17]  T. Luther,et al.  Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. , 1994, The Journal of clinical investigation.

[18]  K. Duffin,et al.  Heterogeneity of plasma tissue factor pathway inhibitor. , 1994, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[19]  R. Hull,et al.  Venous thromboembolism in neurosurgery and neurology patients: a review. , 1994, Neurosurgery.

[20]  W. Kisiel,et al.  Distribution of Tissue Factor Pathway Inhibitor in Normal and Malignant Human Tissues , 1993, Thrombosis and Haemostasis.

[21]  N. Callander,et al.  Immunohistochemical identification of tissue factor in solid tumors , 1992, Cancer.

[22]  A. Lindahl,et al.  Indices of hypercoagulation in cancer as compared with those in acute inflammation and acute infarction. , 1990, Haemostasis.