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Analysis of chromosomal instability in pulmonary or liver metastases and matched primary hepatocellular carcinoma after orthotopic liver transplantation
Author(s) -
GrossGoupil Marine,
Riou Philippe,
Emile JeanFrançois,
Saffroy Raphaël,
Azoulay Daniel,
Lacherade Isabelle,
Receveur Aline,
PiatierTonneau Dominique,
Castaing Denis,
Debuire Brigitte,
Lemoine Antoinette
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11017
Subject(s) - loss of heterozygosity , microsatellite instability , hepatocellular carcinoma , liver transplantation , metastasis , cancer research , pathology , biology , carcinoma , primary tumor , lung , microsatellite , transplantation , medicine , cancer , gene , allele , genetics
To investigate the genetic mechanism of metastatic spread in hepatocellular carcinoma (HCC), we analyzed genomic changes in lung or liver metastases and the corresponding primary tumors (83 tumor samples) in 18 patients who underwent orthotopic liver transplantation. We studied the incidence of microsatellite instability (MSI) and loss of heterozygosity (LOH) involving 8 highly polymorphic microsatellite markers and the polyA tract, Bat26 . We also sought alterations of p53 and β‐catenin gene mutations. High MSI (>30–40% of the loci analyzed) was found only in primary tumors (11%), whereas LOH was observed in 50% of primary and in 39% of recurrent tumors. p53 mutations were found in 2 cases of primary HCC but not in the corresponding metastases. P53 was overexpressed in 4 primary HCC (22%) and 7 metastases (39%). The percentage of β‐catenin gene mutations was low (6%). Lung metastases retained the D16S402 microsatellite abnormalities observed in the primary tumors, whereas recurrent liver tumor did not ( p = 0.02). In conclusion, LOH and P53 protein overexpression, rather than mutations in the p53 or β‐catenin genes or MSI, seem to be involved in the spreading of HCC, suggesting the presence of metastasis suppressor genes in the vicinity of the chromosomal loci in question. © 2003 Wiley‐Liss, Inc.