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Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation cascade and intracellular signaling pathways. It is also involved in malignant processes and has been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathological significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of immunopositivity of tumor cells, patients were divided into “Negative TF” (0%), “Weak TF” (<25%), or “High TF” (25% or more) group. “Negative TF”, “Weak TF”, and “High TF” group accounted for 11.6% (n=13), 44.2% (n=50), and 44.2% (n=50), respectively. Increased TF expression correlated with the extent of the primary tumor (p=0.0043), lymph node metastasis (p=0.0043), the presence of lymphatic distant metastasis (p=0.0039), advanced TNM stage (p=0.0002), and high tumor grade (p=0.0164). Multivariate analysis using Cox’s proportional hazards model showed high TF expression to be an independent negative predictor for survival (hazard ratio, 2.014; p=0.0076) as well as the presence of lymph node metastasis (hazard ratio, 2.953; p=0.0103) or high tumor grade (hazard ratio, 1.882; p=0.0154). Furthermore, to investigate the effect of TF expression on tumor invasiveness, Matrigel invasion assays were performed in a pancreatic cancer cell line transfected with short interfering RNA (siRNA) against TF. TF knockdown by siRNA suppressed the invasiveness in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma through stimulating tumor invasiveness and evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]