Korean J Hepatobiliary Pancreat Surg.  2005 Mar;9(1):16-22.

DNA Hypermethylation and the Loss of Heterozygosity of Chromosome 16q22 in Hepatocellular Carcinoma

Affiliations
  • 1Department of Pathology, Kwandong University College of Medicine, Myongji Hospital, Goyang, Korea.
  • 2Department of Surgery, Hallym University College of Medicine, Seoul, Korea. jskim@hallym.or.kr
  • 3Department of Pathology, Hallym University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
E-cadherin gene, located on chromosome 16q22, may play crucial roles in the cell adhesion and propensity for more malignant properties of various organs. Although loss of heterozygosity (LOH) and DNA hypermethylation at various chromosomal loci have been reported on many malignant tumors, they have been rarely studied in hepatocarcinogenesis, especially for the E-cadherin gene. Our objectives were to evaluate E-cadherin LOH and hypermethylation in hepatocellular carcinomas (HCC) and to correlate with various clinicopathological facors. METHODS: The LOH analysis was performed by using polymerase chain reaction (PCR) with three polymorphic microsatellite markers (D16S419, D16S3106, D16S498) in 40 surgically resected HCCs and each non-tumorous counterpart. The hypermethylation was studied using methylation specific PCR. RESULTS: LOH and hypermethylation were detected in 35% and 55% of HCC, respectively. Also, LOH and hypermethylation were detected in 0% and 32.5% of non-tumor lesions, respectively. LOH results correlated well with higher tumor histologic grade, tumor size and intrahepatic metastasis or vascular tumor invasion. Hypermethylation results correlated well with presence of cirrhosis. Correlation between LOH and hypermethylation was not recognized, but 45.5% of hypermethylation cases showed LOH detection. CONCLUSION: These results suggest that E-cadherin LOH may be associated with more malignant phenotype and tumor progression. And E-cadherin DNA hypermethylation may participates in the early hepatocarcinogenesis by preceding LOH but not causing LOH.

Keyword

Carcinoma, Hepatocellular; Chromosomes, Human, 16; Polymorphism; DNA Methylation; Loss of Heterozygosity

MeSH Terms

Cadherins
Carcinoma, Hepatocellular*
Cell Adhesion
DNA Methylation
DNA*
Fibrosis
Loss of Heterozygosity*
Methylation
Microsatellite Repeats
Neoplasm Metastasis
Phenotype
Polymerase Chain Reaction
Cadherins
DNA
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