Cadherin/catenin complex appears to be intact in hepatocellular carcinomas from Australia and South Africa.
OBJECTIVE
E-cadherin binds to beta-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 beta-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 beta-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, beta-catenin mutations and E-cadherin and beta-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, chi(2)). In contrast, E-cadherin promoter hypermethylation was common in Australian cases in both malignant (30%vs 13%; P = not significant, chi(2)) and non-malignant liver (57%vs 8%, respectively, P < 0.001, chi(2)). Methylation of non-malignant liver was more likely to be detected in patients over the age of 50 years (P < 0.001, chi(2)), the overall mean age for our cohort of patients. Only one beta-catenin mutation was identified. E-cadherin protein expression was reduced in one HCC, while abnormalities in protein expression were absent in beta-catenin.


CONCLUSIONS
Contrary to previous observations in HCC from other countries, neither E-cadherin nor beta-catenin appears to play a role in hepatocarcinogenesis in Australian and South African patients with HCC.
Herath
Nirmitha I
NI
Conjoint Gastroenterology Laboratory, Clinical Research Center, Royal Brisbane Hospital Research Foundation, Brisbane, Australia. nirmithH@qimr.edu.au
Walsh
Michael D
MD
Kew
Michael C
MC
Young
Joanne
J
Leggett
Barbara A
BA
Macdonald
Graeme A
GA
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics; D001315:Australia; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013019:South Africa; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin