Tissue factor, angiogenesis and thrombosis in pancreatic cancer.

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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.