title: Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma.
abstract: BACKGROUND
  Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers.
  
  
  METHODS
  Relevant articles were identified via Ovid medline 1946-2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis.
  
  
  RESULTS
  A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15-3.79), CD3 (HR=0.51, 95% CI=0.32-0.70), CD8 (HR=0.55, CI=0.31-0.80) and EGFR (HR=1.65, 95% CI=1.14-2.16).
  
  
  CONCLUSIONS
  Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK.
authors.forename: L H
authors.initials: LH
authors.lastname: McCormick Matthews
authors.affiliation: 1] Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK [2] Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: F
authors.initials: F
authors.lastname: Noble
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK.
authors.forename: J
authors.initials: J
authors.lastname: Tod
authors.affiliation: Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: E
authors.initials: E
authors.lastname: Jaynes
authors.affiliation: Public Health Sciences and Medical Statistics, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: S
authors.initials: S
authors.lastname: Harris
authors.affiliation: 1] Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK [2] Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: J N
authors.initials: JN
authors.lastname: Primrose
authors.affiliation: 1] Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK [2] National Institute for Health Research, Experimental Cancer Medicine Centre, Southampton SO16 6YD, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ottensmeier
authors.affiliation: 1] Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK [2] Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Thomas
authors.affiliation: 1] Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, MP824, Southampton SO16 6YD, UK [2] Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Underwood
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor