J Korean Med Sci.  2004 Feb;19(1):83-86. 10.3346/jkms.2004.19.1.83.

Detection of Aberrant p16INK4A Methylation in Sera of Patients with Liver Cirrhosis and Hepatocellular Carcinoma

• Chu HJ
• Heo J
• Seo SB
• Kim GH
• Kang DH
• Song GA
• Cho M
• Yang US

• KMID: 1785699
• DOI: http://doi.org/10.3346/jkms.2004.19.1.83

Abstract

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 p16INK4A tumor suppressor gene frequently displays genetic alteration in HCC tissues. The present study was performed to examine the incidence of methylated p16INK4A 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 p16INK4A was evaluated by methylation-specific PCR of serum samples. Methylated p16INK4A was detected in 17.4% (4/23) of LC patients and in 47.8% (22/46) of HCC patients. No association was demonstrated between p16INK4A methylation and serum AFP level. As the status of p16INK4A methylation was not associated with serum AFP level, it may have a role as a tumor marker of HCC.

Keyword

p16INK4A Methylation; PCR, Methylation-Specific; Carcinoma, Hepatocellular; Liver Cirrhosis

MeSH Terms

Aged
Carcinoma, Hepatocellular/*genetics
DNA/metabolism
*DNA Methylation
Female
Fibrosis
*Genes, p16
Human
Liver/pathology
Liver Cirrhosis/*genetics
Liver Neoplasms/*genetics
Male
Middle Aged
Polymerase Chain Reaction
Predictive Value of Tests
Protein p16/*blood
Sensitivity and Specificity
Time Factors
Tumor Markers, Biological

Figure

• 

  Fig. 1 Detection of aberrant p16INK4A methylation (sample numbers 14, 38, 39 and 40, as indicated with arrows) in the sera of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). U, unmethylated; M, methylated; bp, base pairs.

• 

  Fig. 2 Serum AFP levels of 44 HCC patients according to status of p16INK4A methylation.

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