Portions of this study were presented at the annual meeting of the US-Canadian Academy of Pathology, Washington, DC, March 22, 2010
Glutamine synthetase expression in activated hepatocyte progenitor cells and loss of hepatocellular expression in congestion and cirrhosis
Article first published online: 31 JAN 2013
© 2013 John Wiley & Sons A/S
Volume 33, Issue 4, pages 525–534, April 2013
How to Cite
Liver Int. 2013: 33: 525–534
- Issue published online: 12 MAR 2013
- Article first published online: 31 JAN 2013
- Accepted manuscript online: 3 JAN 2013 02:02AM EST
- Manuscript Accepted: 7 DEC 2012
- Manuscript Received: 22 SEP 2012
- congestive heart failure;
- glutamine synthetase;
- progenitor cells;
- stem cells;
Background & Aims
In normal human liver, glutamine synthetase (GS) is expressed in a rim of hepatocytes surrounding hepatic veins. GS expression is decreased in cirrhosis and increased in chronic hepatitis, focal nodular hyperplasia, peritumoural hyperplasia and some hepatocellular neoplasms. For the non-neoplastic conditions, there is limited information available on histological pattern of altered GS expression and the mechanisms of these changes.
We examined GS expression in 58 large specimens and 45 needle biopsies with a variety of non-neoplastic human liver conditions and in 12 normal control livers. Expression was correlated with clinical and histological disease states.
We identified four patterns of GS expression: (i) Loss of normal perivenular expression was seen in states of chronic congestion, severe cirrhosis and zone 3 necrosis. (ii) Diffuse expression was seen in states with active hepatocellular injury and correlated with Ki-67 expression. (iii) Interface expression was seen in feathery degeneration of chronic cholestasis. (iv) GS expression in activated hepatocyte progenitor cells (HPCs) associated with small ducts and ductules was seen in fulminant hepatic failure and in early and late chronic liver disease and rarely in normal livers.
Glutamine synthetase expression is increased in regenerating hepatocytes and in early HPCs prior to morphological evidence of hepatocellular differentiation. This may be the earliest marker of HPCs yet demonstrated. Loss of expression may be a reflection of disrupted endothelium-hepatocyte contact in hepatic vein walls caused by congestive injury as found in congestive heart failure and advanced cirrhosis.