Endothelins and their receptors in cirrhotic and neoplastic livers of Canadian and Chinese populations

Background: Endothelins (ETs) are 21 amino acid peptides with widespread ti ssue distribution and functions. In this study, we retrospectively investig ated immunoreactive ET-I, ET-3 as well as ET receptors by ligand binding an d autoradiography in hepatic cirrhosis and neoplasms. Materials and Methods : Formalin fixed paraffin embedded tissues from 30 hepatocellular carcinoma s (HCC), 4 fibrolamellar carcinomas (FLC), and 7 liver metastatic adenocarc inomas (Ad) from colon were collected from the Pathology Department of Lond on Health Science Centre. Adjacent cirrhotic livers were obtained from 17 c ases and adjacent normal liver was present in 12 cases. In addition, 15 HCC s, 6 cirrhotic and 8 normal livers were obtained from Normal Bethune Univer sity 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 I-125-ET- 1 was carried out in some of the cases. Results : In the normal liver, hepatocytes, biliary epithelium, vascular endotheliu m and smooth muscle cells were positive for both ET-1 and BT-3. Higher immn unoreactivity for ET-1 and ET-3 was seen in cirrhosis. HCCs showed variatio n in immunoreactivity, with overall scoring not different from normal liver s. FLCs showed consistent higher immunoreactivity for both ET-1 and ET-3, w hile in Ads the immunoreactivity was decreased. Increased ET-receptors, rep resenting both ETA and ETB subtypes were seen in both cirrhosis and in HCC, Conclusion: Alterations in both ETs and their receptors were found in cirr hosis and neoplastic liver diseases.