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. 2001 Jan;48(1):80–86. doi: 10.1136/gut.48.1.80

Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma

S Chariyalertsak 1, V Sirikulchayanonta 1, D Mayer 1, A Kopp-Schneider 1, G Furstenberger 1, F Marks 1, K Muller-Decker 1
PMCID: PMC1728157  PMID: 11115827

Abstract

METHODS—Cellular localisation of the cyclooxygenase (COX) isozymes COX-1 and COX-2 was analysed in 24 cholangiocarcinomas, including 17 matched tissues originating from non-tumorous liver tissue adjacent to tumours and seven biopsies of normal human liver, by immunohistochemistry using isozyme selective antibodies.
RESULTS—In normal liver, constitutive expression of COX-2 protein was a characteristic feature of hepatocytes whereas no COX-2 immunosignal was detectable in normal bile duct epithelium, Kupffer, and endothelial cells. In cholangiocarcinoma cells, COX-2 protein was strongly expressed at high frequency. The intensity, percentage of positive cells, and pattern of COX-2 expression were found to be independent of the stage of tumour differentiation. In hepatocytes of matched non-tumorous tissue, COX-2 expression was unaltered. In contrast, strong COX-1 expression was frequently localised to Kupffer cells, endothelial cells, and occasionally to hepatocytes, but not to bile duct epithelial cells. In approximately half of moderately and poorly differentiated but not well differentiated cholangiocarcinomas, weak to moderate COX-1 staining was found in tumour cells while COX-1 expression in Kupffer cells was much more pronounced.
CONCLUSION—Aberrant COX-2 expression occurs during the early stage while COX-1 over expression seems to be related to later stages of cholangiocarcinogenesis.


Keywords: cyclooxygenase; immunohistochemistry; cholangiocarcinoma; bile duct; hepatocyte; Kupffer cell

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Figure 1  .

Figure 1  

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Immunohistochemical localisation of COX-1 in non-tumorous liver tissue and in intrahepatic cholangiocarcinomas at different stages of differentiation. Paraffin sections were stained using polyclonal goat anti-COX-1 antibodies (SC1754). The brown staining represents COX-1 protein. (A-C) Non-tumorous liver tissue. (A) Arrows indicate COX-1 positive Kupffer cells. (B) Arrow indicates a single epithelial cell of the bile duct expressing COX-1. (C) Blood vessel; endothelial cells express COX-1. (D) Well differentiated cholangiocarcinoma. (E) Moderately and (F) poorly differentiated cholangiocarcinomas showing COX-1 immunosignals in epithelial cells of the gland-like structures. Original magnifications: 1:375 (B, D, E, F); 1:725 (A, C).

Figure 2  .

Figure 2  

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Immunohistochemical localisation of COX-2 in non-tumorous liver tissue and in intrahepatic cholangiocarcinomas at different stages of differentiation. Paraffin sections were stained using the polyclonal goat anti-COX-2 antibodies (SC1745). (A) Non-tumorous tissue demonstrating positive COX-2 immunosignals in hepatocytes (open arrow) but not in bile duct epithelial cells (filled arrow). (B, C) Well differentiated, (D) moderately differentiated, and (E, F) poorly differentiated cholangiocarcinomas showing COX-2 immunosignals in epithelial cells of the gland-like structures. Original magnifications: 1:375 (A-F).

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