Genotype stability and clonal evolution of hepatocellular carcinoma assessed by autopsy-based genome-wide microsatellite analysis.

Abstract

It is widely accepted that chromosomal instability is an essential feature of cancer cells including hepatocellular carcinoma (HCC) cells. For an accurate characterization of clonal evolution of HCC cells, we studied chromosomal alterations in various metastatic lesions in an autopsy case of HCC. Tissues from the main tumor, which consisted of 2 macroscopically distinct portions, and from intrahepatic metastasis, portal vein thrombus, epiploic lymph node metastasis, and pulmonary metastasis as well as from the non-tumorous liver were analyzed with comprehensive microsatellite analysis. Alleles showing imbalance of the main tumor were further subjected to comparative duplex PCR, with use of a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. A striking finding was that allelic imbalances detected in the main tumor and metastatic lesions were almost identical, showing -1p, +1q, -4q, -7, -8p, +8q, +9q, +10, -13q, -17p, +19p, -19q, and -X. Additional alterations of +2q and -16q were detected in one portion of the main tumor and the portal vein thrombus. In conclusion, clonal evolution of the HCC cells during metastatic progression seems rare, in contrast to many recurrent chromosomal aberrations that may have accumulated before the clinical manifestation.