Epithelial-mesenchymal transition phenotype is associated with clinicopathological factors that indicate aggressive biological behavior and poor clinical outcomes in invasive breast cancer

Abstract

Purpose: Cancer tissue may display a wide spectrum of ex­pression phenotypes of epithelial-mesenchymal transition (EMT)-related proteins. The purpose of this study was to in­vestigate the clinical significance of EMT phenotypes in breast cancer. Methods: We evaluated the expression pattern of the EMT-related proteins E-cadherin and fibronectin in samples from 1,495 patients with invasive breast carcinoma (IBC) on tis­sue microarrays using immunohistochemistry to investigate the clinical significance of EMT phenotypes in IBC. EMT pheno­types were divided into complete type (E-cadherin-negative/fi­bronectin-positive), incomplete type (hybrid type, E-cadherin-positive/fibronectin-positive; null type, E-cadherin-negative/fi­bronectin-negative), and wild-type (E-cadherin-positive/fibro­nectin-negative). We analyzed the correlation of EMT phenotype with clinicopathological factors and patient survival. Results: Loss of E-cadherin was observed in 302 patients (20.2%), and fibronectin was expressed in the cancer cells of 354 patients (23.7%). In total, 64 (4.3%), 290 (19.4%), 238 (15.9%), and 903 (60.4%) samples were categorized as complete, hybrid, null, and wild-type, respectively. The complete EMT phenotype ex­hibited significant associations with young age (p=0.017), ad­vanced pT (p<0.001) and pN (p<0.001) stages, higher histo­logical grade (p<0.001), lymphovascular invasion (p<0.001), and triple negativity (p<0.001). Patients with complete and hy­brid EMT phenotypes had poorer overall survival (OS) and dis­ease-free survival (DFS) than those with the wild-type pheno­type (OS, p=0.001; DFS, p<0.001). In multivariate analysis, the hybrid EMT phenotype was an independent prognostic factor for DFS in patients with IBC (p=0.032). Conclusion: EMT pheno­types exhibited significant associations with clinicopathological factors indicating aggressive biologic behavior and poor out­come in patients with IBC.