title: Promoter methylation of E-cadherin in hepatocellular carcinomas and dysplastic nodules.
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.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ghee Young
authors.initials: GY
authors.lastname: Kwon
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Cho
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality; D018899:CpG Islands; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000401:mortality; D011401:Promoter Regions, Genetic
chemical_list: D015820:Cadherins