J Korean Med Sci.  2005 Apr;20(2):242-247. 10.3346/jkms.2005.20.2.242.

Promoter Methylation of E-cadherin in Hepatocellular Carcinomas and Dysplastic Nodules

• Kwon GY
• Yoo BC
• Koh KC
• Cho JW
• Park WS
• Park CK

• KMID: 1095198
• DOI: http://doi.org/10.3346/jkms.2005.20.2.242

Abstract

In order to clarify the significance of E-cadherin methylation in multistep hepatocarcinogenesis, we examined the methylation status of the E-cadherin promoter region, using methylation-specific polymerase chain reaction in 64 hepatocellular carcinomas (HCCs) and 13 dysplastic nodules (DNs), and correlated these results with E-cadherin protein expression and clinicopathologic factors of HCCs. Promoter methylation was detected in 1 of 13 (7.7%) DNs, in 5 of 13 (38.5%) Edmondson and Steiner grade I HCCs, and in 27 of 51 (52.9%) grade II or III HCCs, and a significant correlation was observed between the methylation status and the stepwise progression of hepatocarcinogenesis (p=0.004). Reduced E-cadherin immunoreactivity was found in 18 of 64 (28%) HCCs, but in none of DNs. E-cadherin methylation status in HCCs was significantly correlated with microvascular invasion (p=0.02) and tumor recurrence (p=0.04), but not with reduced E-cadherin immunoreactivity. The Kaplan-Meier method showed that methylation status did not have a significant influence on the recurrence-free survival of HCC patients (p=0.15). Our results indicate that methylation of the E-cadherin promoter region is a frequent event in HCC, which may play an important role in the stepwise progression of hepatocarcinogenesis. And the promoter methylation of E-cadherin in HCC was found to be significantly correlated with microvascular invasion and recurrence.

Keyword

Carcinoma, Hepatocellular; Dysplastic Nodule; Cadherins; DNA Methylation

MeSH Terms

Adult
Aged
Cadherins/*genetics
Carcinoma, Hepatocellular/*genetics/mortality
CpG Islands
Female
Humans
Liver Neoplasms/*genetics/mortality
Male
Middle Aged
Precancerous Conditions/*genetics/mortality
Promoter Regions (Genetics)
Research Support, Non-U.S. Gov't

Figure

• 

  Fig. 1 Immunohistochemical analysis of E-cadherin in dysplastic nodule and hepatocellular carcinoma. (A) Maintained E-cadherin immunoreactivity in a dysplastic nodule and adjacent nontumorous liver. (B) Reduced immunoreactivity in hepatocellular carcinoma Edmondson and Steiner grade III. (×100). N, nontumorous liver.

• 

  Fig. 2 Representative examples of methylation-specific PCR analysis of E-cadherin in a dysplastic nodule (DN) and in hepatocellular carcinomas (HCCs). DNA extracted from 77 liver tissues was modified with sodium bisulfite and then amplified with primers specific for the unmethylated (U) or methylated (M) CpG islands of E-cadherin. G, Edmondson and Steiner Grade.

• 

  Fig. 3 Kaplan-Meier curves for recurrence-free survival in 54 patients with HCC according to the methylation status of E-cadherin. Solid line, patients without methylation. Dotted line, patients with methylation.

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