title: Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) is a transient process occurring during developmental stages and carcinogenesis, characterized by phenotypic and molecular alterations, resulting in increased invasive and metastatic capabilities of cancer cells and drug resistance. Moreover, emerging evidence suggests that EMT is associated with increased enrichment of cancer stem-like cells in neoplastic tissues. We interrogated the molecular alterations occurring in breast cancer using proposed EMT markers such as E-cadherin, vimentin, epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF) D, and nuclear factor κ B (NF-κ B) to decipher their roles in the EMT and breast cancer progression.
  
  
  METHODS
  Fifty-seven invasive ductal adenocarcinomas of the breast were assessed for the expression of E-cadherin, vimentin, EGFR, NF-κ B, and PDGF-D using immunohistochemical analysis. Tumors were categorized into three groups: A (ER+, and/or PR+, HER-2/neu-), B (ER+, and/or PR+, HER-2/neu+), and C (triple-negative: ER-, PR-, and HER-2/neu-). Immunostained slides were microscopically evaluated and scored using intensity (0, 1+, 2+, and 3+) and percentage of positive cells, and data were statistically analyzed.
  
  
  RESULTS
  Membranous E-cadherin was positive in all 57 cases (100%), whereas cytoplasmic E-cadherin was predominantly positive in groups B and C compared with group A (21%, 7%, and 0%, respectively). All group A cases were negative for vimentin and EGFR. There was statistically significant increased expression of vimentin (P < .0002), EGFR (P < .0001), and NF-κ B (P < .02) in triple-negative cases when compared with groups A and B.
  
  
  CONCLUSIONS
  Vimentin, EGFR, and NF-κ B were significantly increased in triple-negative tumors, which is consistent with the aggressiveness of these tumors. These markers could be useful as markers for EMT in breast cancers and may serve as predictive markers for designing customized therapy in the future.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. sethis@karmanos.org
authors.forename: Seema
authors.initials: S
authors.lastname: Sethi
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Quratulain
authors.initials: Q
authors.lastname: Ahmed
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Zeina A
authors.initials: ZA
authors.lastname: Nahleh
authors.forename: Assaad
authors.initials: A
authors.lastname: Semaan
authors.forename: Wael
authors.initials: W
authors.lastname: Sakr
authors.forename: Adnan
authors.initials: A
authors.lastname: Munkarah
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi