Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer.
OBJECTIVE
Hemostatic activation is common in pancreatic cancer and may be linked to angiogenesis and venous thromboembolism. We investigated expression of tissue factor (TF), the prime initiator of coagulation, in noninvasive and invasive pancreatic neoplasia. We correlated TF expression with vascular endothelial growth factor (VEGF) expression, microvessel density, and venous thromboembolism in resected pancreatic cancer.


METHODS
Tissue cores from a tri-institutional retrospective series of patients were used to build tissue microarrays. TF expression was graded semiquantitatively using immunohistochemistry in normal pancreas (n=10), intraductal papillary mucinous neoplasms (n=70), pancreatic intraepithelial neoplasia (n=40), and resected or metastatic pancreatic adenocarcinomas (n=130).


RESULTS
TF expression was observed in a majority of noninvasive and invasive pancreatic neoplasia, including 77% of pancreatic intraepithelial neoplasias, 91% of intraductal papillary mucinous neoplasms, and 89% of pancreatic cancers, but not in normal pancreas. Sixty-six of 122 resected pancreatic cancers (54%) were found to have high TF expression (defined as grade >or=2, the median score). Carcinomas with high TF expression were more likely to also express VEGF (80% versus 27% with low TF expression, P<0.0001) and had a higher median MVD (8 versus 5 per tissue core with low TF expression, P=0.01). Pancreatic cancer patients with high TF expression had a venous thromboembolism rate of 26.3% compared with 4.5% in patients with low TF expression (P=0.04).


CONCLUSIONS
TF expression occurs early in pancreatic neoplastic transformation and is associated with VEGF expression, increased microvessel density, and possibly clinical venous thromboembolism in pancreatic cancer. Prospective studies evaluating the role of TF in pancreatic cancer outcomes are warranted.
Khorana
Alok A
AA
James P. Wilmot Cancer Center, Department of Medicine, University of Rochester, Rochester, New York 14642, USA. alok_khorana@URMC.rochester.edu
Ahrendt
Steven A
SA
Ryan
Charlotte K
CK
Francis
Charles W
CW
Hruban
Ralph H
RH
Hu
Ying Chuan
YC
Hostetter
Galen
G
Harvey
Jennifer
J
Taubman
Mark B
MB
D000368:Aged; D002196:Capillaries; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality*; D016019:Survival Analysis; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020246:Venous Thrombosis / Q000209:etiology*
D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin