title: Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours.
abstract: Neuroendocrine tumours (NETs) of the lung represent a wide spectrum of phenotypically distinct entities, with differences in tumour progression and aggressiveness. The redistribution and/or the loss of various cell adhesion molecules, such as the E-cadherin-catenin complex, play a predominant role in carcinogenesis and in tumour invasion. Moreover, mutations in exon 3 of the beta-catenin gene, the adenomatous polyposis coli (APC) gene or the E-cadherin genes were previously found to result in intracytoplasmic and/or nuclear beta-catenin protein accumulation, activating nuclear transcription of target genes involved in tumour progression. In the present study, the distribution of the components of this E-cadherin-catenin complex has been investigated by immunohistochemistry and an attempt has been made to correlate the abnormal expression pattern with the eventual detection of mutations in the corresponding genes. This study included 27 primary NETs of the lung, with nine typical carcinoids (TCs), three atypical carcinoids (ACs), and 15 large cell neuroendocrine carcinomas (LCNECs). The E-cadherin-catenin complex remained expressed in most of these lung tumours, but with a cytoplasmic and/or nuclear redistribution of beta-catenin, E-cadherin, and alpha-catenin; abnormal positive immunoreactivity was observed in 24 (88.9%), in 21 (80.8%), and in 20 (76.9%) NETs, respectively. In the great majority of cases, there was a good correlation between the expression of these three proteins, but no significant association with histological classification or TNM stage. Thus, E-cadherin-complex redistribution cannot be considered a prognostic marker in NET of the lung. Of particular interest was the frequent focal beta-catenin nuclear immunostaining (55.5% in total), which was also unrelated to histological type or TNM stage. However, this study failed to detect any mutation in exon 3 of the beta-catenin gene, in the APC gene or in the E-cadherin gene. These data suggest another mechanism of regulation of beta-catenin in these tumours.
authors.affiliation: INSERM Unit U. 514, I.F.R. 53 and Laboratoire Pol Bouin, 45 Rue Cognacq-Jay, Hospital Maison Blanche, 51092 Reims, France. cclavel@chu-reims.fr
authors.forename: C E
authors.initials: CE
authors.lastname: Clavel
authors.forename: F
authors.initials: F
authors.lastname: Nollet
authors.forename: G
authors.initials: G
authors.lastname: Berx
authors.forename: S
authors.initials: S
authors.lastname: Tejpar
authors.forename: B
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.forename: H H
authors.initials: HH
authors.lastname: Kaplan
authors.forename: F M
authors.initials: FM
authors.lastname: van Roy
authors.forename: P L
authors.initials: PL
authors.lastname: Birembaut
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017491:Genes, APC; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin