1. ¹Laboratory of Breast and Gynecological Cancer, Molecular Pathology Program, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
2. ²Service of Pathology, Hospital Clinico Universitario, Salamanca, Spain
3. ³Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Correspondence: José Palacios, M.D., Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), c./Melchor Fernández Almagro n° 3, 28029 Madrid, Spain. fax: 34-91-224-69-23; e-mail: jpalacios@cnio.es.

Accepted 28 March 2003.

Abstract

Pleomorphic lobular carcinoma of the breast is a variant of infiltrating lobular carcinoma that has poor prognosis. The pleomorphic appearance of this variant hinders its correct identification and differentiation from ductal carcinoma. The analysis of E-cadherin glycoprotein expression is a powerful tool for distinguishing lobular from ductal carcinomas, because complete loss of E-cadherin expression occurs in most infiltrating lobular tumors and lobular carcinomas in situ, but not in ductal tumors. In the present study, we have evaluated E-cadherin expression by immunohistochemistry in a series of 29 pleomorphic lobular breast carcinomas, including 7 cases with an in situ component. Complete loss of E-cadherin expression was observed in all the cases (29/29, 100%), in invasive and in situ components. To understand better the mechanisms underlying E-cadherin inactivation in this tumor type, the frequency of loss of heterozygosity at the E-cadherin gene locus (16q22.1) was analyzed. All informative tumors (27/27, 100%) showed loss of heterozygosity, thus implying a strong association between loss of E-cadherin expression and loss of heterozygosity at 16q22.1. Moreover, loss of heterozygosity was detected in all in situ components analyzed. These results imply that in terms of E-cadherin inactivation, pleomorphic lobular tumors are identical to classic infiltrating lobular carcinomas and distinct from ductal tumors, and therefore they should be considered a variant of lobular carcinoma of the breast, despite their aggressive behavior.