Tissue Factor and Hematological Neoplasias

Abstract 5132

There is a well- recognized correlation between cancer and aberrant hemostasis. Venous thromboembolism (VTE) in individuals with solid epithelial tumors has been associated with a poor prognosis, with more than three-fold higher risk of early death as compared to cancer patients without thrombosis. The expression of tissue factor (TF), a cell-surface membrane glycoprotein that triggers the activation of coagulation by cancer cells, is one of the main underlying mechanisms linking thrombosis and aggressive tumor behavior. TF is expressed in a variety of solid tumors in association with genetic events affecting oncogenes and tumor suppressor genes. However, the mechanisms of thrombosis in individuals with hematological malignancies may differ from those with solid tumors. We have previously shown that despite the high rate of thrombosis in multiple myeloma, malignant plasma cells only rarely express TF. We sought to determine TF gene (F3) and protein expression in hematological neoplasias. F3 expression profiling was studied on a variety of cell lines established from lymphoid and myeloid neoplasias available at Glaxo Smith Kline (GSK) Cancer Cell Line Genomic Profiling Dataset (https://array.nci.nih.gov/caarray/project/woost-00041). Interestingly, F3 expression was absent in all lymphoid neoplasias studied, in sharp contrast to acute myeloid leukemias (AML) and solid tumors, of which 30 and 90% expressed F3, respectively. Immunohistochemistry (IHC) confirmed the absence of TF protein expression in all indolent and high-grade B-cell lymphomas (99 patients, including germinal center and activated B-cell phenotype diffuse large B-cell lymphomas) and in all T-cell lymphomas/leukemias (20 patients) studied. IHC for TF was also negative in AML (11 patients) but positive in representative solid tumors (breast, pancreas, prostate), except for renal cell carcinoma which has been previously shown to lack TF. We propose that the pathogenesis of VTE associated with hematological neoplasias differs from that of solid tumors. Though TF from non-neoplastic cell sources may still be important for the prothrombotic state often seen in these patients, we show there is no evidence for a role of tumor-derived TF in the development of DVT, nor in neoplastic behavior. Thus, treatments directed against TF may not impact on prognosis in lymphoid, and non TF-expressing myeloid neoplasias.