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Cholestasis is a marker for hepatocellular carcinomas displaying β-catenin mutations

Authors

  • V Audard,

    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
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    • These authors contributed equally to this work.

  • G Grimber,

    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
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    • These authors contributed equally to this work.

  • C Elie,

    1. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    2. Service de Biostatistique et d'Informatique Médicale, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • B Radenen,

    1. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    2. Service d'Anatomie et de Cytologie Pathologiques, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • A Audebourg,

    1. Service d'Anatomie et de Cytologie Pathologiques, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • F Letourneur,

    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
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  • O Soubrane,

    1. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    2. Service de Chirurgie Digestive, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • M-C Vacher-Lavenu,

    1. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    2. Service d'Anatomie et de Cytologie Pathologiques, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • C Perret,

    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
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  • C Cavard,

    Corresponding author
    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    • Institut Cochin, Département EMC, Paris, F-75014, France.
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  • B Terris

    1. Institut Cochin, Département EMC, Paris, F-75014, France
    2. INSERM U567, Paris, F-75014, France
    3. CNRS, UMR-S 8104, Paris, F-75014, France
    4. Faculté de Médecine René Descartes Paris 5, UM3, Paris, F-75006, France
    5. Service d'Anatomie et de Cytologie Pathologiques, Hôpital Cochin, AP-HP, Paris, F-75014, France
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  • No conflicts of interest were declared.

Abstract

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.

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