title: Epithelial-Mesenchymal Transition Phenotype Is Associated with Clinicopathological Factors That Indicate Aggressive Biological Behavior and Poor Clinical Outcomes in Invasive Breast Cancer.
abstract: OBJECTIVE
  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-cadherinpositive/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).
  
  
  CONCLUSIONS
  EMT phenotypes exhibited significant associations with clinicopathological factors indicating aggressive biologic behavior and poor outcome in patients with IBC.
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Bae
authors.affiliation: Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Su Hwan
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
keywords: Breast neoplasms; Epithelial-mesenchymal transition; Prognosis