title: Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.
abstract: OBJECTIVE
  The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria.
  
  
  RESULTS
  A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR = 0.31, 95% CI: 0.71-0.56), Bcl-2 (HR = 0.41, 95% CI: 0.27-0.63), survivin (HR = 0.46, 95% CI: 0.29-0.73), Ki-67: (HR = 2.42, 95% CI: 1.87-3.14), COX-2 (HR = 1.39, 95% CI: 1.13-1.71), E-cadherin (HR = 1.80, 95% CI: 1.33-2.42), and S100 calcium-binding proteins, in particular S100A2 (HR = 3.23, 95% CI: 1.58-6.62).
  
  
  CONCLUSIONS
  We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms.
authors: West of Scotland Pancreatic Unit and Department of Pathology, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, United Kingdom.
authors: Nigel B
authors: NB
authors: Jamieson
authors: C Ross
authors: CR
authors: Carter
authors: Colin J
authors: CJ
authors: McKay
authors: Karin A
authors: KA
authors: Oien
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D014018:Tissue Distribution; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor