Zacharski L R, Memoli V A, Rousseau S M, Kisiel W
Department of Medicine, Dartmouth Medical School, White River Junction, Vermont.
Cancer. 1987 Dec 1;60(11):2675-81. doi: 10.1002/1097-0142(19871201)60:11<2675::aid-cncr2820601117>3.0.co;2-c.
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.
通过免疫组织化学技术,在肺小细胞癌新鲜冰冻切片中原位鉴定了凝血因子。凝血酶原/凝血酶、因子VII、因子X和抗凝血酶III存在于细胞间隙并与肿瘤细胞相关。因子IX、因子XI、前激肽释放酶和高分子量激肽原被鉴定与肿瘤细胞相关,但不存在于细胞间隙。对于因子V、因子VIII相关抗原、因子XII、因子XIII的B亚基、α1-抗胰蛋白酶、α2-巨球蛋白或α2-抗纤溶酶,观察到可变的结缔组织染色,但未观察到与肿瘤相关的染色。连续组织和肿瘤均未表现出血小板Ib和IIbIIIa表面糖蛋白。这些不同的染色模式表明,检测到的凝血因子并非仅仅从通透性血管中扩散而来,而是在原位选择性定位。虽然肿瘤组织内可能存在既抑制又促进凝血酶生成的条件,但我们认为观察到的凝血因子之间的相互作用最终导致局部凝血酶形成,这是肺小细胞癌中已描述的明显纤维蛋白沉积的原因。局部形成的凝血酶可能有助于这种肿瘤的进展。华法林治疗对局部凝血酶形成的抑制作用可以解释华法林治疗在治疗肺小细胞癌中的有益效果。