Tissue factor, angiogenesis and thrombosis in pancreatic cancer.

Average: 6 (1 vote)

2006 ASCO Annual Meeting


Abstract No: 4001


Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 4001


Author(s):A. A. Khorana, C. W. Francis, C. K. Ryan, M. B. Taubman, Y. C. Hu, S. A. Ahrendt


Background: Coagulation proteins are commonly activated in pancreatic cancer and are closely linked to regulation of angiogenesis. We investigated tumor cell expression of tissue factor (TF), the prime initiator of coagulation, and its association with parameters of angiogenesis, venous thromboembolism (VTE) and survival.

Methods: Tissue cores from a bi-institutional retrospective series of patients consecutively resected between January 1994 and February 2002 and followed for a median period of 16 months were used to build a pancreatic cancer tissue microarray. TF expression was graded semiquantitatively using immunohistochemistry (IHC)(grade 0:negative, grade 1: 1- 33% positive, grade 2: 34- 66% positive and grade 3: > 66% cells positive) in pancreatic intraductal dysplasia (n=5) and resected pancreatic cancer (n=122). Study endpoints included correlation of TF with VEGF expression by IHC, microvessel density (MVD), clinical VTE and survival in resected patients. Patients with history of VTE, on anticoagulation or with inadequate follow-up were excluded from analysis of VTE outcomes (n=33).

Results: TF expression was observed in all specimens with intraductal dysplasia and 108 resected pancreatic cancers (89%) but not in uninvolved pancreas. Sixty-six patients (54%) with resected pancreatic cancer were found to have high TF expression (defined as > grade 2, the median score), and 56 patients (46%) had low or no TF expression. Tumors with high TF expression were more likely to also express VEGF (80% versus 27% with low TF expression, p<0.0001). Tumors with high TF expression had a higher median MVD (8 versus 5/tissue core with low TF expression, p=0.01). Resected patients with high TF expression had a VTE rate of 20% compared to 5.5% in patients with low TF expression (p=0.04). Median survival in tumors with high TF was 17.9 months versus 12.6 months in those with low TF (p=0.16).

Conclusions: TF expression appears to occur early in pancreatic cancer pathogenesis. This is the first report describing an association of TF expression with VEGF expression, increased MVD and clinical VTE in resected pancreatic cancer, confirming the linkage of thrombosis and angiogenesis. Targeting TF in pancreatic cancer could affect both neoplastic and thrombotic outcomes.