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Cadherin/catenin complex appears to be intact in hepatocellular carcinomas from Australia and South Africa
Author(s) -
HERATH NIRMITHA I,
WALSH MICHAEL D,
KEW MICHAEL C,
YOUNG JOANNE,
LEGGETT BARBARA A,
MACDONALD GRAEME A
Publication year - 2004
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2004.03361.x
Subject(s) - loss of heterozygosity , cadherin , hepatocellular carcinoma , catenin , methylation , dna methylation , medicine , immunohistochemistry , cancer research , cohort , pathology , beta catenin , gastroenterology , oncology , biology , cell , dna , gene , gene expression , wnt signaling pathway , genetics , allele
Background and Aim: E‐cadherin binds to β‐catenin to form the cadherin/catenin complex required for strong cell adhesion. Inactivation of this complex in tumors facilitates invasion into surrounding tissues. Alterations of both proteins have been reported in hepatocellular carcinomas (HCC). However, the interactions between E‐cadherin and β‐catenin in HCC from different geographical groups have not been explored. The aim of the present study was to assess the role of E‐cadherin and β‐catenin in Australian and South African patients with HCC. Methods: DNA was extracted from malignant and non‐malignant liver tissue from 37 Australian and 24 South African patients, and from histologically normal liver from 20 transplant donors. Chromosomal instability at 16q22, promoter methylation at E‐cadherin , β‐catenin mutations and E‐cadherin and β‐catenin protein expression was assessed using loss of heterozygosity, methylation‐specific polymerase chain reaction, denaturing high‐performance liquid chromatography and immunohistochemistry, respectively. Results: Loss of heterozygosity at 16q22 was prevalent in South African HCC patients (50% vs 11%; P < 0.05, χ 2 ). In contrast, E‐cadherin promoter hypermethylation was common in Australian cases in both malignant (30% vs 13%; P = not significant, χ 2 ) and non‐malignant liver (57% vs 8%, respectively, P < 0.001, χ 2 ). Methylation of non‐malignant liver was more likely to be detected in patients over the age of 50 years ( P < 0.001, χ 2 ), the overall mean age for our cohort of patients. Only one β‐catenin mutation was identified. E‐cadherin protein expression was reduced in one HCC, while abnormalities in protein expression were absent in β‐catenin. Conclusion: Contrary to previous observations in HCC from other countries, neither E‐cadherin nor β‐catenin appears to play a role in hepatocarcinogenesis in Australian and South African patients with HCC.