Liver Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2005; 11(30): 4638-4643
Published online Aug 14, 2005. doi: 10.3748/wjg.v11.i30.4638
Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: Possible role in tumor promotion and angiogenesis
Melchiorre Cervello, Daniela Foderà, Ada Maria Florena, Maurizio Soresi, Claudio Tripodo, Natale D’Alessandro, Giuseppe Montalto
Melchiorre Cervello, Daniela Foderà, Institute of Biomedicine and Molecular Immunology “Alberto Monroy”, National Research Council, Palermo, Italy
Ada Maria Florena, Claudio Tripodo, Institute of Pathologic Anatomy, University of Palermo, Palermo, Italy
Maurizio Soresi, Giuseppe Montalto, Department of Clinical Medicine, University of Palermo, Palermo, Italy
Natale D’Alessandro, Department of Pharmacological Science, University of Palermo, Palermo, Italy
Author contributions: All authors contributed equally to the work.
Supported by the MIUR and Progetto Strategico Oncologia “Terapia Preclinica Moleculare Oncologia” MIUR-CNR
Correspondence to: Melchiorre Cervello, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, C.N.R., Via Ugo La Malfa 153, Palermo 90146, Italy. cervello@ibim.cnr.it
Telephone: +39-91-6809534 Fax: +39-91-6809548
Received: July 26, 2004
Revised: November 1, 2004
Accepted: November 4, 2004
Published online: August 14, 2005
Abstract

AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous (NT) tissues.

METHODS: Immunohistochemistry for COX-2, CD34, CD68 and mast cell tryptase (MCT) was performed on 14 well-characterized series of liver-cirrhosis-associated HCC patients. COX-2 expression and the number of inflammatory cells in tumor lesions and surrounding liver tissues of each specimen were compared. Moreover, COX-2, CD34 staining and the number of inflammatory cells in areas with different histological degrees within each tumor sample were comparatively analyzed.

RESULTS: The percentage of COX-2 positive cells was significantly higher in NT tissues than in tumors. COX-2 expression was higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast cells were observed within the tumor mass, whereas a higher number was observed in the surrounding tissue, especially in peri-portal spaces of NT tissues. Abundant macrophages/ Kupffer cells were observed in NT tissues, whereas the number of cells was significantly lower in the tumor mass. However, a higher cell number was observed in the well-differentiated tumor and progressively decreased in relation to the differentiation grade. Within the tumor, a positive correlation was found between COX-2 expression and the number of macrophages/Kupffer cells and mast cells. Moreover, there was a positive correlation between CD34 and COX-2 expression in tumor tissues. Comparison between well- and poorly-differentiated HCC showed that the number of CD34-positive cells decreased with dedifferentiation. However, COX-2 was the only independent variable showing a positive correlation with CD34 in a multivariate analysis.

CONCLUSION: The presence of inflammatory cells and COX-2 expression in liver tumor suggests a possible relationship with tumor angiogenesis. COX-2 expressing cells and the number of macrophages/Kupffer cells and mast cells decrease with progression of the disease.

Keywords: COX-2, HCC, Angiogenesis, Mast cells, Macro-phages