Carcinogenesis Advance Access originally published online on December 4, 2003
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Carcinogenesis, Vol. 25, No. 4, 541-547,
April 2004
Carcinogenesis vol.25 no.4 © Oxford University Press 2004; all rights reserved.
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Microsatellite instability mutator phenotype in hepatocellular carcinoma in non-alcoholic and non-virally infected normal livers
1 Service de Biochimie et Biologie Moléculaire, 2 Centre Hépato-biliaire and 3 Anatomie Pathologique, Hôpital Paul Brousse, Assistance Publique–Hôpitaux de Paris and 4 INSERM U268, IFR 89, Faculté de Médecine Paris-Sud, Université Paris XI, 14 Avenue Paul Vaillant Couturier, 94804 Villejuif Cedex, France and 5 Pfizer, Centre de Recherche, 37401 Amboise, France
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 on in our hospital between 1984 and 2001. We analyzed 37 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 conference consensus workshop for colorectal cancer. High MSI (MSI-H > 30%) was found in 6 (16%) and low MSI (MSI-L < 30%) in 10 (27%) of the 37 HCCs. 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 tumors which can be considered as a new clinical/histological entity.