title: Expression of protease-activated receptors and tissue factor in human liver.
abstract: Thrombin, acting via protease-activated receptors (PARs), and tissue factor (TF) are involved in inflammation, tissue repair and tumorigenesis. Hepatocellular carcinomas (HCCs) usually complicate chronic liver diseases characterised by inflammation and fibrosis. The aim of this study was to describe the expression of PARs and TF in normal liver, cirrhosis and HCCs. We performed an immunohistochemical detection of PAR-1, PAR-3, PAR-4 and human TF in human tissue samples from 19 subnormal livers, 33 cirrhosis and 30 HCCs. PAR-1 was found on endothelial cells of sinusoids and larger vessels. In cirrhosis, spindle-shaped cells within septa and T lymphocytes were PAR-1 positive. A few PAR-1-positive tumour cells were found in 10% of HCCs. PAR-4 expression was restricted to macrophages, B lymphocytes and nerves. PAR-3 expression was rare. Unexpectedly, TF was expressed in 95% of normal livers and in 94% of cirrhosis but only in 50% of HCCs (p<0.001). Staining was mostly hepatocellular. No association existed between TF labelling and clinicopathological characteristics of HCCs. In conclusion, the pattern of expression of PARs is compatible with its role in chronic liver disease by promoting inflammation via immune cells and neurogenic stimulation. However, our data do not support a role for PARs or TF in HCC progression.
authors.affiliation: GREF/INSERM E362, Université Victor Segalen Bordeaux 2, 146, Rue Léo Saignat, Bordeaux 33076, France. anne.rullier@chu-bordeaux.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Rullier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Senant
authors.forename: Walter
authors.initials: W
authors.lastname: Kisiel
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.forename: Charles
authors.initials: C
authors.lastname: Balabaud
authors.forename: Brigitte
authors.initials: B
authors.lastname: Le Bail
authors.forename: Jean
authors.initials: J
authors.lastname: Rosenbaum
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044462:Receptors, Proteinase-Activated / Q000096:biosynthesis*; D013925:Thromboplastin / Q000096:biosynthesis*
chemical_list: D044462:Receptors, Proteinase-Activated; D013925:Thromboplastin