Occurrence of blood coagulation factors in situ in small cell carcinoma of the lung.
Through immunohistochemical techniques, blood coagulation factors were identified in situ in fresh frozen sections of small cell carcinoma of the lung. Prothrombin/thrombin, factor VII, factor X, and antithrombin III were present in intercellular spaces and associated with tumor cells. Factor IX, factor XI, prekallikrein, and high molecular weight kininogen were identified as being associated with tumor cells but did not exist in intercellular spaces. Variable connective tissue staining but no tumor-related staining was observed for factor V, factor VIII-related antigen, factor XII, the B subunit of factor XIII, alpha 1-antitrypsin, alpha 2-macroglobulin, or alpha 2-antiplasmin. Neither consecutive tissue nor the tumor manifested platelet Ib and IIbIIIa surface glycoproteins. These divergent staining patterns suggested that the detected clotting factors had not merely diffused from permeabilized blood vessels, but were selectively localized in situ. While conditions may exist within tumor tissue that both retard and promote thrombin generation, we propose that interactions between the observed coagulation factors ultimately lead to local thrombin formation, which is responsible for the conspicuous fibrin deposits already described in small cell carcinoma of the lung. Thrombin formed locally might contribute to progression of this tumor. Inhibition of local thrombin formation by warfarin therapy could explain the beneficial effects of warfarin therapy in treating small cell carcinoma of the lung.
Zacharski
L R
LR
Department of Medicine, Dartmouth Medical School, White River Junction, Vermont.
Memoli
V A
VA
Rousseau
S M
SM
Kisiel
W
W
D000941:Antigens / Q000032:analysis; D000990:Antithrombin III / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000032:analysis*; D018288:Carcinoma, Small Cell / Q000097:blood*; D005164:Factor IX / Q000032:analysis; D005169:Factor VIII / Q000032:analysis / Q000276:immunology; D005342:Fibrinolysis; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood*; D013917:Thrombin / Q000096:biosynthesis; D014841:von Willebrand Factor
D000941:Antigens; D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D000990:Antithrombin III; D005169:Factor VIII; D005164:Factor IX; D013917:Thrombin