Tissue Factor Is Frequently Expressed in Multiple Myeloma Cells.

Abstract 2132

Poster Board II-109

Tissue factor (TF) is a 47 kDa transmembrane glycoprotein that initiates blood coagulation when complexed with factor VIIa. TF is constitutively expressed in a variety of tumor cells and has been shown to have a role in cellular signaling, angiogenesis and solid tumor progression. However, the role of TF in the hematologic malignancies is poorly defined. Multiple myeloma (MM) is associated with an increased risk of venous thromboembolic disease. However, whether increased TF expression contributes to the hypercoagulable state associated with MM remains controversial. In this study, we determined the expression of TF on archived bone marrow biopsies and plasmacytomas, and human MM cell lines. Immunohistochemical staining of TF was carried out on paraffin-embedded specimens from eighteen advanced stage MM patients. Staining for TF expression was scored as 0 (null), 1+ (weak), 2+ (moderate) and 3+ (strong). TF expression for the MM cell lines (U266B1, MM1.RL and MM1.S) was carried out by semi-quantitative real time RT-PCR. TF mRNA levels were normalized to 18S ribosomal mRNA levels. The TF: 18S ratios were then compared to that of a low TF expressing human breast cancer cell line cell line, MCF-7. Paraprotein distribution in the MM patient specimens was: IgG kappa (7), IgG lambda (5), IgA kappa (3), lambda light chain (2) kappa light chain (1). Overall, TF expression was observed in 10/18 (56%) of the patient specimens. Six specimens stained 1+, and two each stained 2+ and 3+. Staining was mainly cytoplasmic and did not correlate with the type of secreted paraprotein. TF expression (relative to MCF-7) was 17.3, 1.97 and 0.77 for the U266B1, MM1.RL and MM1.S cell lines, respectively. Results from these studies suggest that TF is frequently expressed in MM cells and might contribute to the hypercoagulability associated with this disease. In addition, TF may play a role in MM cell progression.