Detection of aberrant p16INK4A methylation in Sera of patients with liver cirrhosis and hepatocellular carcinoma

Hepatocellular carcinomas (HCCs) show genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and chromosomal amplification. The genes most frequently involved are those encoding tumor suppressors. The p16(INK4A) tumor suppressor gene frequently displays genetic alteration in HCC tissues. The present study was performed to examine the incidence of methylated p16(INK4A) in the sera of liver cirrhosis (LC) and HCC patients, and to evaluate its role as a tumor marker of HCC. The sera of 23 LC patients and 46 HCC patients were examined in this study. The methylation status of p16(INK4A) was evaluated by methylation-specific PCR of serum samples. Methylated p16(INK4A) was detected in 17.4% (4/23) of LC patients and in 47.8% (22/46) of HCC patients. No association was demonstrated between p16(INK4A) methylation and serum AFP level. As the status of p(16INK4A) methylation was not associated with serum AFP level, it may have a role as a tumor marker of HCC.