Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma.
OBJECTIVE
Recent studies have shown that tissue factor (TF) may be involved in tumor angiogenesis and metastasis. The role of TF in hepatocellular carcinoma (HCC) was unknown. This study evaluated whether TF expression correlates with microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, tumor invasiveness, and prognosis in human HCC.


METHODS
Tissue samples were obtained from 58 specimens of resected HCC. Immunohistochemical expression of TF was examined, and tumor MVD was evaluated using CD34 as the endothelial marker. TF and VEGF protein levels in the tumor cytosol were quantified by ELISA. Clinicopathologic and follow-up data of patients were prospectively collected.


RESULTS
The immunohistochemical expression of TF in the tumors correlated significantly with tumor MVD (P = 0.002). The median cytosolic TF protein level in the tumors was 720 pg/mg total protein (range, 67-2406 pg/mg total protein). A significant positive correlation was found between TF and VEGF levels in the tumor cytosol (r = 0.475, P < 0.001). High tumor cytosolic TF level was associated with venous invasion (P = 0.004), microsatellite nodules (P = 0.024), unencapsulated tumor (P = 0.007), and advanced tumor stage (P = 0.010). A higher than median tumor cytosolic TF level was an independent predictor of poor survival (risk ratio, 1.836; 95% confidence interval 1.130-5.312, P = 0.023).


CONCLUSIONS
This study shows that TF is related to tumor angiogenesis and invasiveness in HCC. Evaluation of tumor TF expression may be useful as a prognostic indicator in patients with HCC.
Poon
Ronnie Tung-Ping
RT
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. poontp@hkucc.hku.hk
Lau
Cecilia Pik-Yuk
CP
Ho
Joanna Wen-Ying
JW
Yu
Wan-Ching
WC
Fan
Sheung-Tat
ST
Wong
John
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D013925:Thromboplastin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin