title: Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.
abstract: OBJECTIVE
  The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients.
  
  
  METHODS
  Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and beta-catenin were assessed with the use of immunohistochemistry.
  
  
  RESULTS
  Immunohistochemistry revealed a lack of expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma.
  
  
  CONCLUSIONS
  These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.
authors.affiliation: Cell and Molecular Biology Laboratory, Robert E Wise Research and Education Institute, Burlington, MA 01805, USA. Kimberly.R.Christ@lahey.org
authors.forename: K M
authors.initials: KM
authors.lastname: Rieger-Christ
authors.forename: J A
authors.initials: JA
authors.lastname: Pezza
authors.forename: J M
authors.initials: JM
authors.lastname: Dugan
authors.forename: J W
authors.initials: JW
authors.lastname: Braasch
authors.forename: K S
authors.initials: KS
authors.lastname: Hughes
authors.forename: I C
authors.initials: IC
authors.lastname: Summerhayes
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; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin