title: Expression of APC, β-catenin and E-cadherin in Tunisian patients with gastric adenocarcinoma: clinical significance.
abstract: Aberrant activation of the Wnt signalling pathway is a key feature of many cancers. β-Catenin, adenomatous polyposis coli (APC) and E-cadherin are major players in this pathway. The aim of this study is to examine the expression of β-catenin, APC and E-cadherin in tumour tissues of 80 Tunisian patients with gastric carcinoma and to determine the methylation status of the APC promoter in tumour tissues. Associations between protein expression and clinico-pathological parameters, including prognosis, were performed. Positive expression of β-catenin, APC and E-cadherin was observed in 77.5, 68.7 and 60% of cases, respectively. Tumours lacking membranous expression of β-catenin had greater extent of lymph node metastasis, poor differentiation and advanced T-stage. The expression of E-cadherin correlated with poor differentiation (P = 0.05) and β-catenin expression (P = 0.004). With regards to prognosis, the overall survival time was significantly prolonged for patients showing normal β-catenin expression (exclusively or predominantly membranous staining) alone or combined with positive APC expression (P log rank = 0.008 and 0.003, respectively). The methylated pattern of APC promoter 1A was detected in 43.8% of cases and correlated with T-stage (P = 0.046) and distant metastasis (P = 0.037). No correlation was found between the methylated profile of APC promoter 1A and the expression of APC protein in tumour tissues. Our findings suggest that deregulation of the Wnt pathway via abnormal expression of β-catenin and E-cadherin occurred frequently in gastric carcinoma and correlated with worse clinical behaviour.
authors.affiliation: Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour Street Km 6, BP 1177, 3038, Sfax, Tunisia.
authors.forename: Dorra Ben
authors.initials: DB
authors.lastname: Ayed-Guerfali
authors.forename: Basma
authors.initials: B
authors.lastname: Hassairi
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014416:Tunisia; D055815:Young Adult; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin