These authors contributed equally to this work.
Cholestasis is a marker for hepatocellular carcinomas displaying β-catenin mutations†
Article first published online: 9 MAY 2007
Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 212, Issue 3, pages 345–352, July 2007
How to Cite
Audard, V., Grimber, G., Elie, C., Radenen, B., Audebourg, A., Letourneur, F., Soubrane, O., Vacher-Lavenu, M.-C., Perret, C., Cavard, C. and Terris, B. (2007), Cholestasis is a marker for hepatocellular carcinomas displaying β-catenin mutations. J. Pathol., 212: 345–352. doi: 10.1002/path.2169
No conflicts of interest were declared.
- Issue published online: 4 JUN 2007
- Article first published online: 9 MAY 2007
- Manuscript Accepted: 25 FEB 2007
- Manuscript Revised: 7 FEB 2007
- Manuscript Received: 21 NOV 2006
- Ligue Nationale contre le Cancer
- hepatocellular carcinoma;
- glutamine synthetase;
- bile acids
The Wnt/β-catenin signalling pathway is activated in many human hepatocellular carcinomas (HCC). Identification of β-catenin mutation relies mostly on sequence analysis and/or immunohistochemistry. β-catenin mutation may also be detected by analysing the expression of its target genes. The GLUL gene encoding glutamine synthetase (GS), for example, appears to be a pertinent marker. The aim of this study was to correlate GS immunostaining and β-catenin mutations with clinicopathological features in HCC. We found that GS immunostaining had a sensitivity of 90% for the detection of β-catenin mutations, with 98% specificity, whereas β-catenin immunostaining had a sensitivity of 63% with 98% specificity. We used the sensitive GS marker to characterize 190 HCC cases. Sixty-eight (36%) cases displayed Wnt/β-catenin activation. In addition to their well-differentiated pattern, these tumours exhibited significant features such as a homogeneous microtrabeculo-acinar pattern, low-grade cellular atypia, and cholestasis. As these tumours exhibited cholestasis, we hypothesized that β-catenin acts on specific bile synthesis and/or transport pathways. In conclusion, we propose that GS immunostaining and a cholestatic pattern are relevant criteria for the identification of HCC with β-catenin mutations. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.