Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas

Aims-The relation between lobular carcinoma in situ (LCIS) and invasive bre ast cancer is unresolved. In an attempt to establish whether LCIS is a prec ursor of invasive cancer the mutational status and the expression of E-cadh erin was analysed in LCIS and associated invasive breast carcinoma in 23 pa tients. Methods-Foci of LCIS and associated invasive carcinoma were individually mi crodissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gen e were analysed using single strand conformation polymorphism (SSCP); prote in expression and the localisation of E-cadherin and beta -catenin were ass essed with the use of immunohistochemistry. Results-Immunohistochemistry revealed a lack of expression of E-cadherin an d beta -catenin in most LCIS samples and invasive foci. In all but four cas es, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta -catenin was also undetected, sugge sting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive c arcinoma were not identified in this series of patients. However, mutationa l 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. Conclusion-These data support the hypothesis that LCIS is not a precursor o f invasive breast carcinoma but a marker of increased risk of developing in vasive disease.