Glutamine Synthetase (GS) Expression in Cirrhosis, Veno-Occlusive Disease (VOD), Congested Liver Adjacent to Mass Lesions, and Focal Nodular Hyperplasia (FNH)
KE Fleming, IR Wanless. Dalhousie University, Halifax, NS, Canada
Background: In normal liver, GS is expressed in a narrow rim of perivenous hepatocytes. In cirrhotic human liver GS expression was undetectable in one study (Racine-Samson 1996). In another study GS expression was present in a perivenous pattern within cirrhotic nodules or at the periportal interface when hepatic veins (HVs) were adherent to a septum (DiTommaso 2007, Rebouissou 2008). We have noted many hepatic veins in cirrhotic nodules do not have perivenous GS expression. The purpose of this study is to clarify the patterns and mechanisms of GS expression, including the loss of GS staining in some perivenous regions in cirrhosis and other liver conditions.
Design: Surgically resected specimens of liver with a variety of conditions were studied after staining serial sections for connective tissue (trichrome), GS, and CD34. Specimens included cirrhosis removed at transplantation (alcohol 6, NASH 1, HCV 5, biliary cirrhosis 5), congenital hepatic fibrosis (1), tissue adjacent to mass lesions (4), VOD (2), chronic cholestasis without cirrhosis (1), and FNH (4).
Results: We confirmed the perivenous GS pattern in cirrhosis as described by DiTommaso et al. and the map-like increase in perivenous expression in FNH reported by Bioulac-Sage et al. 2009. In addition, we noted GS positive hepatocytes within nascent cirrhotic nodules within septa (buds). GS was absent adjacent to approximately one third to half of HVs within cirrhotic nodules, most of which were also CD34 negative. GS negative HVs were especially prominent in highly regressed cirrhosis. GS staining was also lost in areas of congestive injury, especially in congested cirrhotic nodules and in non-cirrhotic liver adjacent to mass lesions, in VOD, and in congested regions of FNH.
Conclusions: GS staining is lost during the acute phase of congestive zone 3 injury. HVs in highly regressed cirrhosis are often GS negative and CD34 negative. We interpret these HVs as recruited veins remodeled from sinusoidal structures, supporting the suggestion that cirrhosis regresses as new HV outflow capacity is generated. Buds arising from paraductal tissue are GS positive and appear to give rise to small GS positive nodules in advanced micronodular cirrhosis.
Category: Liver & Pancreas
Monday, March 22, 2010 1:00 PM
Poster Session II # 175, Monday Afternoon