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

K M Rieger-Christ^1,*, J A Pezza^1,*, J M Dugan², J W Braasch¹, K S Hughes³ and I C Summerhayes¹

¹ Cell and Molecular Biology Laboratory, Robert E Wise Research and Education Institute, 31 Mall Road, Burlington MA 01805, USA
² Department of Pathology, Lahey Clinic, 41 Mall Road Burlington, MA 01805, USA
³ Department of General Surgery, Lahey Clinic

Correspondence to:
Dr Rieger-Christ Kimberly.R.Christ{at}lahey.org

Aims—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 ß-catenin were assessed with the use of immunohistochemistry.

Results—Immunohistochemistry revealed a lack of expression of E-cadherin and ß-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, ß-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.

Conclusion—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.

Key Words: lobular carcinoma in situ • breast • E-cadherin • infiltrating lobular carcinoma

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Reis-Filho, J. S, Pinder, S. E (2007). Non-operative breast pathology: lobular neoplasia. J. Clin. Pathol. 60: 1321-1327 [Abstract] [Full Text]  
• Chuba, P. J., Hamre, M. R., Yap, J., Severson, R. K., Lucas, D., Shamsa, F., Aref, A. (2005). Bilateral Risk for Subsequent Breast Cancer After Lobular Carcinoma-In-Situ: Analysis of Surveillance, Epidemiology, and End Results Data. JCO 23: 5534-5541 [Abstract] [Full Text]