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

Kwon, Ghee Young    (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.   ); Yoo, Byung Chul    (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.   ); Koh, Kwang Cheol    (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.   ); Cho, Jae Won    (Department of General Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.   ); Park, Won Sang    (Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.   ); Park, Cheol Keun    (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.  );
  • 초록

    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.


  • 주제어

    Carcinoma, Hepatocellular .   Dysplastic Nodule .   Cadherins .   DNA Methylation.  

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