Clinical and Biological Significance of E-cadherin Protein Expression in Invasive Lobular Carcinoma of the Breast

Background: Although virtually all cases of lobular carcinoma in situ lack E-cadherin expression, a proportion of morphologically typical invasive lobular carcinomas (ILCs) retain its expression. The frequency and significance of E-cadherin expression in ILC remain to be elucidated. In this study, we have assessed E-cadherin protein expression in a well-characterized series of histologically defined ILC (239 cases) with a long-term clinical follow-up to determine the frequency, clinical and biological significance of its expression. E-cadherin-positive ILCs (ILC+) were subsequently examined to assess the expression of component members of the E-cadherin membrane complex (E-cadherin, p120, alpha, beta, and gamma-catenins) to determine its integrity. Results: Thirty-eight ILC cases (16%) showed positive E-cadherin expression (ILC+). Membranous expression of E-cadherin was mainly circumferential with frequent coexisting perimembranous cytoplasmic expression. No association between E-cadherin expression and any of the clinicopathologic variables, immunophenotype, or tumor behavior was identified, apart from an association with lobular histologic subtype and vascular invasion. Analysis of the E-cadherin-catenin complex showed abnormal expression of one or more of the catenin complex members in the majority of cases. The most frequent observation was the diffuse cytoplasmic expression of catenins, in particular p120, which showed similar expression to that reported in E-cadherin-negative ILCs. Conclusions: These results provide evidence that E-cadherin is expressed in a proportion of ILC, however, unlike ductal carcinoma, its expression seems to be of limited significance and it is usually associated with evidence of impaired integrity of the E-cadherin-catenin membrane complex. Our data offer a possible explanation for the presence but lack functionality of E-cadherin in some cases of ILC and imply that immunohistochemical expression of E-cadherin per se in ILC histologic phenotypic tumors should not preclude its diagnosis.