title: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ.
abstract: Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and gamma-catenin, were studied in a series of 38 lobular breast carcinomas with known E-cadherin mutation status. The effect of loss of E-cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane-associated E-cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non-sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E-cadherin and alpha- and beta-catenin expression was found; in 50 per cent of these cases, additional loss of gamma-catenin was observed. In six invasive lobular carcinomas, expression of both E-cadherin and catenins was retained. In none of these carcinomas was an E-cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E-cadherin and catenins in all the cases studied--remarkably, also, in four cases positive for E-cadherin and catenin expression in the invasive component. These results indicate that simultaneous loss of E-cadherin and alpha-, beta- and gamma-catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer. Events additional to E-cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma.
authors.affiliation: Department of Pathology, Leiden University Medical Center, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: De Leeuw
authors.forename: G
authors.initials: G
authors.lastname: Berx
authors.forename: C B
authors.initials: CB
authors.lastname: Vos
authors.forename: J L
authors.initials: JL
authors.lastname: Peterse
authors.forename: M J
authors.initials: MJ
authors.lastname: Van de Vijver
authors.forename: S
authors.initials: S
authors.lastname: Litvinov
authors.forename: F
authors.initials: F
authors.lastname: Van Roy
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D051180:Desmoplakins; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin