Microparticle‐associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features

Background Patients with pancreatic cancer have an unfavourable prognosis. A central role in pancreatic cancer progression has been suggested for tissue factor ( TF ), the main initiator of the blood coagulation cascade. We hypothesized that elevated levels of plasma microparticle ( MP )‐associated TF activity might indicate the presence of poorly differentiated pancreatic cancer, disease dissemination and infiltration of peripancreatic vessels. Methods MP ‐ TF activity was measured in 73 pancreatic cancer patients and 22 healthy controls. Abdominal computerized tomography ( CT ) scans performed at study inclusion were investigated for probability of tumoural vascular invasion. In addition, intratumoural TF expression, D ‐dimer and CA 19‐9 levels were determined. Results MP ‐ TF activity (pg/mL) was significantly higher in patients (median: 0·37 [range: 0·00–11·91]) than in controls (median: 0·05 [range: 0·00–0·76]; P  < 0·001). When pancreatic cancer patients were compared with regard to stage and grade, significantly elevated levels of MP ‐ TF activity were only present in those with poorly differentiated metastatic nonresectable tumours ( n  = 11, median: 2·95 [range: 0·25–11·91]). In three patients with poorly differentiated tumours, a high probability of vascular invasion was found ( MP ‐ TF activity in these cases: 2·95, 7·00 and 10·34). MP ‐ TF activity correlated strongly with CA 19‐9 (r = 0·60) and weakly with D ‐dimer (r = 0·33) levels. Immunohistochemical staining for TF was positive in 14 of 15 resected tumours. MP ‐ TF activity was associated with an increased risk of mortality ( HR : 1·8 per doubling in MP ‐ TF activity, [95% CI : 1·4–2·4, P  < 0·001]). Conclusion MP ‐ TF activity might represent a biomarker for a poorly differentiated and invasive pancreatic cancer phenotype and poor survival.