Immunohistochemical detection of HCV in cirrhosis, dysplastic nodules, andhepatocellular carcinomas with parallel-tissue quantitative RT-PCR

Hepatitis C virus is a major risk factor for hepatocarcinogenesis in humans . In situ detection of the virus in early sequential lesions of hepatocarci nogenesis could provide information about the role of the virus in the tran sformation and promotion process. Parallel in situ detection of HCV protein s and RNA in human tissues were performed in 55 posthepatitis C cirrhosis, 17 dysplastic nodules (DN), and 25 hepatocellular carcinomas (HCC), using i nmnunohistochemistry and tissue quantitative RT-PCR A consistent cytoplasmi c hepatocellular staining was obtained in 73% of cirrhosis cases (with or w ithout HCC) and in 55% DN cases. A few tumoral hepatocytes were unambiguous ly stained in 28% HCC. The percentage of positive cells and the intensity o f immunostaining significantly decreased from cirrhosis to HCC through DN, whereas there was no difference in the prevalence of positivity or the numb er of viral copies between cirrhosis and HCC using tissue-quantitative RT-P CR, Finally, RT-PCR levels were found parallel with the immunostaining in c irrhosis but not in HCC. These results suggest that HCV protein synthesis m ay persist but be down-regulated during sequential hepatocarcinogenesis. A putative role of HCV proteins on cell proliferation and differentiation dur ing the early steps of carcinogenesis cannot therefore be excluded.