DISTRIBUTION OF TISSUE FACTOR PATHWAY INHIBITOR IN NORMAL AND MALIGNANT HUMAN TISSUES

Specific antibodies to tissue factor pathway inhibitor (TFPI) were use d in immunohistochemical procedures to determine the distribution of T FPI in normal and neoplastic human tissues. TFPI was restricted to meg akaryocytes and the endothelium of the microvasculature in normal and abnormal tissues, but was not found in the endothelium of larger vesse ls or in hepatocytes. TFPI was also detected in macrophages in the vil li of term placenta. Tumor-associated macrophages in several types of malignancy that we have shown previously to express a complete tissue factor-initiated pathway of coagulation and thrombin generation also m anifested TFPI. By contrast, malignant cells in small cell carcinoma o f the lung, renal cell carcinoma, and malignant melanoma that we have shown previously to express coagulation factors together with tumor ce ll-associated fibrin formation failed to stain for TFPI. We postulate that TFPI may be lacking from the latter malignancies because of the a bsence of the appropriately configured tissue factor - factor VIIa - f actor Xa complex required for TFPI binding.