Endothelins and their receptors in cirrhotic and neoplastic livers of Canadian and Chinese populations
Endothelins (ETs) are 21 amino acid peptides with widespread tissue distribution and functions. In this study, we retrospectively investigated immunoreactive ET-1, ET-3 as well as ET receptors by ligand binding and autoradiography in hepatic cirrhosis and neoplasms. Formalin fixed paraffin embedded tissues from 30 hepatocellular carcinomas (HCC), 4 fibrolamellar carcinomas (FLC), and 7 liver metastatic adenocarcinomas (Ad) from colon were collected from the Pathology Department of London Health Science Centre. Adjacent cirrhotic livers were obtained from 17 cases and adjacent normal liver was present in 12 cases. In addition, 15 HCCs, 6 cirrhotic and 8 normal livers were obtained from Normal Bethune University for Medical Sciences in China. The slides were stained for ET-1 and ET-3 with a polyclonal antibody and scored. Autoradiographic localization of ET-receptors with 125I-ET-1 was carried out in some of the cases. In the normal liver, hepatocytes, biliary epithelium, vascular endothelium and smooth muscle cells were positive for both ET-1 and ET-3. Higher immnunoreactivity for ET-1 and ET-3 was seen in cirrhosis. HCCs showed variation in immunoreactivity, with overall scoring not different from normal livers. FLCs showed consistent higher immunoreactivity for both ET-1 and ET-3, while in Ads the immunoreactivity was decreased. Increased ET-receptors, representing both ETA and ETB subtypes were seen in both cirrhosis and in HCC. Alterations in both ETs and their receptors were found in cirrhosis and neoplastic liver diseases.