Tissue factor (TF) is a transmembrane
glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of
cancer cells. In order to examine the clinicopathologic 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
tumor cell immunopositivity, patients were divided into "negative TF" (0%), "weak TF" (<25%), or "high TF" (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary
tumor (P = 0.0043),
lymph node metastasis (P = 0.0043), lymphatic distant
metastasis (P = 0.0039), advanced
tumor-node-
metastasis stage (P = 0.0002), and high
tumor grade (P = 0.0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative
tumors had a significantly better prognosis even if
lymph node metastasis was present (P < 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic
adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal
adenocarcinoma by stimulating
tumor invasiveness, and that evaluation of the primary
tumor for TF expression may identify patients with a poor prognosis.