Liver Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2005; 11(13): 1896-1902
Published online Apr 7, 2005. doi: 10.3748/wjg.v11.i13.1896
Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma
Terence C. Tang, Ronnie T. Poon, Cecilia P. Lau, Dan Xie, Sheung Tat Fan
Terence C. Tang, Ronnie T. Poon, Cecilia P. Lau, Sheung Tat Fan, Centre for the Study of Liver Disease, and Department of Surgery, the University of Hong Kong, Pokfulam, Hong Kong, China
Dan Xie, Department of Clinical Oncology, the University of Hong Kong, Pokfulam, Hong Kong, China
Author contributions: All authors contributed equally to the work.
Supported by the Sun C.Y. Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong
Correspondence to: Dr. Ronnie T. Poon, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. poontp@hkucc.hku.hk
Telephone: +852-28553641 Fax: +852-28175475
Received: August 18, 2004
Revised: August 20, 2004
Accepted: October 6, 2004
Published online: April 7, 2005
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Cyclooxygenase-2; Vascular endothelial growth factor; Hepatocellular carcinoma