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  • Title: Hepatocarcinogenesis in non-cirrhotic liver is associated with a reduced number of clonal hepatocellular patches in non-tumorous liver parenchyma.
    Author: Adam AC, Faudou V, Paschen SA, Adam OM, Kahl P, Drebber U, Fischer HP, Büttner R.
    Journal: J Pathol; 2012 Nov; 228(3):333-40. PubMed ID: 22685011.
    Abstract:
    We investigated circumscribed cell proliferations in healthy livers in comparison to non-cirrhotic livers bearing hepatocellular carcinoma. Using histochemical staining for cytochrome c oxidase, the fourth complex of the respiratory chain, we visualized patch-forming descendents of regeneratively active liver cells. The clonal nature of these patches was verified by laser-capture microdissection and Sanger sequencing of the enzyme's core subunits in patches carrying marker mutations on the mtDNA. We demonstrate a highly significant increase of the patch size and also a highly significant increase in the number of patches carrying marker mutations between hepatocellular carcinoma-free and -bearing livers. Thus, the carcinoma-bearing livers accumulated more genetic damage on mtDNA than the control group. Furthermore, for the first time, we present evidence in hepatocellular carcinoma-bearing non-cirrhotic livers of a significantly reduced pool of regeneratively active liver cells that are genetically and functionally altered. The analogy to ageing-related changes is suggestive of premature ageing of stem cells in non-cirrhotic hepatocellular carcinoma-bearing liver as an early step to hepatocarcinogenesis.
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