title: The role of biological markers of epithelial to mesenchymal transition in oesophageal adenocarcinoma, an immunohistochemical study.
abstract: BACKGROUND
  E-cadherin, β-catenin, epidermal growth factor receptor (EGFR), neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to mesenchymal transition (EMT). However, the prognostic significance of EMT markers in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate the prognostic value of, and the association between different EMT markers in OAC.
  
  
  METHODS
  Tumour cores of 154 patients with OAC were included in a tissue microarray. Scoring criteria was based on immunohistochemical staining intensity.
  
  
  RESULTS
  EMT-associated markers were expressed in OAC: reduced membranous E-cadherin and β-catenin were seen in 11.4% and 51.7%, nuclear β-catenin in 19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours. Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation was seen between membranous β-catenin and E-cadherin expression (R=0.209, p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate analysis, EGFR overexpression and membranous β-catenin staining were significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218, p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR 1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear β-catenin (HR 1.322; 95% CI 0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851; p=0.968) were not associated with survival. In multivariate analysis, EGFR overexpression was an independent prognostic factor for poor survival (HR 1.678; 95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to 5.576; p=0.005).
  
  
  CONCLUSIONS
  This study supports the presence of EMT in OAC. Moreover, EGFR overexpression was independently associated with a poor survival.
authors: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: M J D
authors: MJ
authors: Prins
authors: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: J P
authors: JP
authors: Ruurda
authors: Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: M P
authors: MP
authors: Lolkema
authors: Department of Surgery, Medical University of Lublin, Lublin, Poland.
authors: R
authors: R
authors: Sitarz
authors: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: F J W
authors: FJ
authors: Ten Kate
authors: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: R
authors: R
authors: van Hillegersberg
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D016009:Chi-Square Distribution; D019938:Cyclin D1 / Q000032:analysis; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000032:analysis; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D051176:beta Catenin / Q000032:analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C513384:CDH1 protein, human; C050361:CDH2 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: ADHESION; CANCER; GASTROINTESTINAL DISEASE; GI NEOPLASMS; IMMUNOHISTOCHEMISTRY