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Carcinogenesis Advance Access published online on December 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgh035
© 2003 by Oxford University Press
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© 2003 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Microsatellite instability mutator phenotype in hepatocellular carcinoma in non alcoholic and non virally infected normal livers

Franck Chiappini 1, Marine Gross-Goupil 2, Raphaël Saffroy 2, Daniel Azoulay 3, Jean-François Emile 4, Luc-Antoine Veillhan 5, Valérie Delvart 5, Stephan Chevallier 6, Henri Bismuth 5, Brigitte Debuire 2, and Antoinette Lemoine 2*

1 Service de Biochimie et Biologie moléculaire, Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris, France; INSERM U268, IFR 89, Faculté de Médecine Paris-Sud, Université Paris XI, 14 avenue Paul Vaillant Couturier - 94804 Villejuif Cedex, France; PFIZER, Centre de Recherche, 37401 Amboise, France
2 Service de Biochimie et Biologie moléculaire, Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris, France; INSERM U268, IFR 89, Faculté de Médecine Paris-Sud, Université Paris XI, 14 avenue Paul Vaillant Couturier - 94804 Villejuif Cedex, France
3 Centre Hépato-biliaire, Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris, France; INSERM U268, IFR 89, Faculté de Médecine Paris-Sud, Université Paris XI, 14 avenue Paul Vaillant Couturier - 94804 Villejuif Cedex, France
4 Anatomie pathologie, Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris, France; INSERM U268, IFR 89, Faculté de Médecine Paris-Sud, Université Paris XI, 14 avenue Paul Vaillant Couturier - 94804 Villejuif Cedex, France
5 Centre Hépato-biliaire, Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris, France
6 PFIZER, Centre de Recherche, 37401 Amboise, France

* Corresponding author. E-mail: antoinette.lemoine{at}pbr.ap-hop-paris.fr.

Received 19 June 2003 ; revised 1 October 2003 ; accepted 17 November 2003

Abstract

Microsatellite instability (MSI) seems to be a rare event in hepatocarcinogenesis and might actually be associated with the progression of hepatocellular carcinoma (HCC) in which the liver is often the site of chronic hepatitis or cirrhosis. The aim of this work was to define the MSI phenotype in HCC affecting exclusively normal livers to avoid slippage errors due to cirrhosis. One hundred and sixty-four patients with HCC affecting non-cirrhotic livers were operated in our hospital between 1984 and 2001. We analyzed 37 consecutive patients selected for low alcohol consumption and the absence of HBV or HCV infection. All the livers were histologically normal. MSI was analyzed according to the criteria defined during the Amsterdam conference consensus workshop for colorectal cancer. High-MSI (MSI-H>30%) was found in 6 (16%) and low-MSI (MSIL<30%) in 10 (27%) of the 37 HCC. None of the 10 microsatellite markers tested were altered in the remaining 21 tumors (57%). Immunohistochemistry showed that normal amounts of hMLH1 and hMSH2 were present both in MSI-H and in MSI-L HCCs. MSI-H was significantly associated with more aggressive histological tumor features and a shorter median delay before recurrence. Thus, we have found a small subgroup of HCC tumorswhich can be considered as a new clinical/histological entity.


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