Fibrinogen-fibrin transformation in situ in renal cell carcinoma.
The mechanism of coagulation activation in renal cell carcinoma was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary tumors. Tissue factor antigen was detected in the endothelium of vascular channels within the tumors. Fibrinogen and factor V were distributed diffusely in the perivascular tumor connective tissue. Fibrin was readily detected in a linear pattern along the edges of nodules of viable tumor indicating that thrombin had formed from the interaction of coagulation factors demonstrated previously in renal cell carcinoma tissue. Tissue plasminogen activator was detected in the endothelium of blood vessels in the vicinity of the tumor and urokinase in areas of necrosis but neither were associated with viable tumor cells. These results indicate that thrombin is formed locally in renal cell carcinoma tissue that transforms fibrinogen to fibrin. There also appears to be a net deficit in fibrinolysis in situ in this tumor. We postulate that these conditions might contribute to stabilization and progression of renal cell carcinoma and that clinical trials of antithrombotic agents are justified in this tumor type.
Wojtukiewicz
M Z
MZ
Department of Medicine, Dartmouth Medical School, Vermont.
Zacharski
L R
LR
Memoli
V A
VA
Kisiel
W
W
Kudryk
B J
BJ
Rousseau
S M
SM
Stump
D C
DC
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005165:Factor V / Q000378:metabolism; D005337:Fibrin / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D010960:Plasminogen Activators / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D011498:Protein Precursors; D005165:Factor V; D005337:Fibrin; D005340:Fibrinogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator