Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma.
OBJECTIVE
Recent studies suggested that cyclooxygenase-2 (COX-2) enhances tumor angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Although COX-2 expression has been demonstrated in hepatocellular carcinoma (HCC), the significance of COX-2 in progression of HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationship with VEGF level in HCC.


METHODS
Fresh tumor tissues were obtained from 100 patients who underwent resection of HCC. COX-2 protein expression was examined by immunohistochemistry, and quantitatively by an enzyme immunometric assay (EIA) of tumor cytosolic COX-2 levels. Tumor cytosolic VEGF levels were measured by an ELISA.


RESULTS
Immunostaining showed expression of COX-2 in tumor cells. Tumor cytosolic COX-2 levels correlated with VEGF levels (r = 0.469, P<0.001). Correlation with clinicopathological features showed significantly higher tumor cytosolic COX-2 levels in the presence of multiple tumors (P = 0.027), venous invasion (P = 0.030), microsatellite lesions (P = 0.037) and advanced tumor stage (P = 0.008). Higher tumor cytosolic COX-2 levels were associated with worse patient survival.


CONCLUSIONS
This study shows that elevated tumor COX-2 levels correlate with elevated VEGF levels and invasiveness in HCC, suggesting that COX-2 plays a significant role in the progression of HCC.
Tang
Terence-C
TC
Center for the Study of Liver Disease, Department of Surgery, University of Hong Kong, Pokfulam, Hong Kong, China.
Poon
Ronnie-T
RT
Lau
Cecilia-P
CP
Xie
Dan
D
Fan
Sheung-Tat
ST
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases