Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.
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.
Rieger-Christ
K M
KM
Cell and Molecular Biology Laboratory, Robert E Wise Research and Education Institute, Burlington, MA 01805, USA. Kimberly.R.Christ@lahey.org
Pezza
J A
JA
Dugan
J M
JM
Braasch
J W
JW
Hughes
K S
KS
Summerhayes
I C
IC
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
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin