E‐cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes

Abstract

Categorizing breast neoplasia as ductal or lobular is a daily exercise that relies on a combination of histologic and immunohistochemical tools. The historically robust link between loss of the E‐cadherin molecule and lobular neoplasia has rendered staining for E‐cadherin by immunohistochemistry a staple of this diagnostic process. Unfortunately, discordances between E‐cadherin expression and histomorphology, and variations in E‐cadherin staining patterns and intensities abound in clinical practice, but are often neglected in favour of a binary interpretation of the E‐cadherin result. In this article, we highlight the complexities of E‐cadherin expression through a review of the E‐cadherin protein and its associated gene (CDH1), the mechanisms leading to aberrant/absent E‐cadherin expression, and the implications of these factors on the reliability of the E‐cadherin immunohistochemical stain in the classification of ductal versus lobular mammary neoplasia.