title: Expression of coagulation factors and their receptors in tumor tissue and coagulation factor upregulation in peripheral blood of patients with cerebral carcinoma metastases.
abstract: BACKGROUND
  Patients with malignancies often suffer from thrombembolic events that complicate the course of cancer disease and reduce the patients' quality of life or shorten the survival time in severe cases. This phenomenon is also known for patients with primary or secondary brain tumors; but the reasons are not identified.
  
  
  METHODS
  We performed a prospective case-controlled study of patients with brain metastases but without any active peripheral tumor site. Blood of patients was collected perioperatively and investigated for coagulation factor activities. Moreover, we analyzed the expression of coagulation factors and their receptors within the tumor material of brain metastases from clear-cell renal cell carcinomas and small-cell carcinomas of the lung.
  
  
  RESULTS
  Here, we show that even patients without an active peripheral tumor disease that means without any tumor masses outside the central nervous system after anticancer treatment by surgery, radiation therapy, or chemotherapy but with symptomatic brain metastasis develop an increased systemic activation of multiple coagulation factors. The pro-coagulatory state is expressed preoperatively, but also can be observed in the early postoperative period. Additionally to that, intracerebral metastases of clear-cell renal cell carcinomas and of small-cell carcinomas of the lung express prothrombin, thrombin, factor X, and the protease-activated receptors type 1, 2, 3, and 4.
  
  
  CONCLUSIONS
  These observations support the hypothesis of a link between the hemostatic system in the periphery and the malignant tumor disease even when the tumor is an intracerebral metastasis and the affected patient currently is free of a systemically active tumor. The results of this study support the hypothesis that the concerted action of coagulation factors and their receptors within the metastasis tissue itself and the systemic coagulation system could control the malignant behavior of tumor disease and make larger prospective trials mandatory.
authors: Department of Neurosurgery, Medical Center of Friedrich-Schiller-University, University Hospital Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors: Jan
authors: J
authors: Walter
authors: Linn L
authors: LL
authors: Handel
authors: Michael
authors: M
authors: Brodhun
authors: Denise
authors: D
authors: van Rossum
authors: Uwe-Karsten
authors: UK
authors: Hanisch
authors: Lutz
authors: L
authors: Liebmann
authors: Frank
authors: F
authors: Heppner
authors: Roland
authors: R
authors: Goldbrunner
authors: Arend
authors: A
authors: Koch
authors: Susanne A
authors: SA
authors: Kuhn
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000096:biosynthesis; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000097:blood* / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000097:blood / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000097:blood / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044462:Receptors, Proteinase-Activated / Q000096:biosynthesis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D044462:Receptors, Proteinase-Activated; C036309:fibrin fragment D; D000990:Antithrombin III; D005340:Fibrinogen