Epithelial-to-Mesenchymal Transition in Metaplastic Breast Carcinomas With Chondroid Differentiation

Abstract

Epithelial-to-mesenchymal transition (EMT) is a key process in tumor progression and is induced by the master regulator Snail, a transcription factor that down-regulates epithelial genes, including E-cadherin, and up-regulates mesenchymal genes. Metaplastic breast carcinomas with chondroid differentiation (MBCD) have an epithelial and a mesenchymal chondroid component, giving them morphologic features reminiscent of EMT. To determine whether EMT plays a role in MBCD, we differentially analyzed Snail and E-cadherin expression in 12 tumors by immunohistochemistry. The interface between the tumor components showed a transition from inactive cytoplasmic Snail expression in the carcinoma component to active nuclear Snail expression in the metaplastic cells. Membranous E-cadherin staining was present in the epithelial and absent in the metaplastic component, showing a gradual loss of expression at the interface. E-cadherin expression was inversely correlated with active nuclear Snail expression. Our results suggest that EMT is induced in MBCD and may contribute to their frequent hematogenous metastasis.