Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma

Methods-Cellular localisation of the cyclooxygenase (COX) isozymes COX-1 an d COX-2 was analysed in 24 cholangiocarcinomas, including 17 matched tissue s originating from non-tumorous liver tissue adjacent to tumours and seven biopsies of normal human liver, by immunohistochemistry using isozyme selec tive antibodies. Results-In normal liver, constitutive expression of COX-2 protein was a cha racteristic feature of hepatocytes whereas no COX-2 immunosignal was detect able in normal bile duct epithelium, Kupffer, and endothelial cells. In cho langiocarcinoma cells, COX-2 protein was strongly expressed at high frequen cy. The intensity, percentage of positive cells, and pattern of COX-2 expre ssion were found to be independent of the stage of tumour differentiation. In hepatocytes of matched nontumorous tissue, COX-2 expression was unaltere d. 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 diff erentiated but not well differentiated cholangiocarcinomas, weak to moderat e COX-1 staining was found in tumour cells while COX-1 expression in Kupffe r cells was much more pronounced. Conclusion-Aberrant COX-2 expression occurs during the early stage while CO X-1 over expression seems to be related to later stages of cholangiocarcino genesis.