Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: possible role in tumor promotion and angiogenesis.
OBJECTIVE
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 (MC(T)) 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.


CONCLUSIONS
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.
Cervello
Melchiorre
M
Istituto di Biomedicina e Immunologia Molecolare Alberto Monroy, Palermo 90146, Italy. cervello@ibim.cnr.it
Foderàa
Daniela
D
Florena
Ada Maria
AM
Soresi
Maurizio
M
Tripodo
Claudio
C
D'Alessandro
Natale
N
Montalto
Giuseppe
G
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007728:Kupffer Cells / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases