title: Aberrant p16INK4A methylation: Relation to viral related chronic liver disease and hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island within the promoter region.
  
  
  OBJECTIVE
  To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis.
  
  
  METHODS
  This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ(2)) test was performed. Exact test was used instead when the expected frequency was less than 5.
  
  
  RESULTS
  Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 μg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size.
  
  
  CONCLUSIONS
  Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC.
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Fatma A
authors.initials: FA
authors.lastname: El-Mougy
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Youssef
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Dalia A
authors.initials: DA
authors.lastname: Omran
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Sahar A
authors.initials: SA
authors.lastname: Sharaf
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Hany H
authors.initials: HH
authors.lastname: El-Sayed
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Walaa A
authors.initials: WA
authors.lastname: Rabie
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Elghobary A
authors.initials: EA
authors.lastname: Mohamed
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Elghobary
keywords: Hepatocellular carcinoma; methylation; p16INK4A