APEX1 and neoplasm: Although in the present study APE1/Ref-1 resulted over-expressed in all HCC specimens, more than half of patients showed an up-regulation also in DLC, suggesting that APE1/Ref-1 transcriptional activation is already present in the earliest phase of liver disease progression, when oxidative burst is elevated and selection of hepatocyte clones able to survive plays a central role in tumor development.