title: Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers.
abstract: Better prognostic information for resected extrahepatic cholangiocarcinoma could guide treatment strategies and potentially improve outcome. This study performed a systematic review and meta-analysis to identify prognostic biomarkers for further investigation.
  
  
  METHODS
  Relevant literature was identified using Medline, EMBASE and Web of Science. Primary end point was overall survival assessed on univariate analysis. Log hazard ratio and variance were calculated and pooled using a random effects inverse variance approach. Hazard ratio and 95% confidence intervals were calculated.
  
  
  RESULTS
  Thirty-seven studies, including 2371 patients, met the inclusion criteria. Subsequently nine biomarkers predictive of OS were identified (HR, 95% CI): VEGF (2.32, 1.57-3.44), COX-2 (1.94, 1.01-3.71), GLUT-1 (2.09, 1.52-2.89), Cyclin D1 (1.96, 1.02-3.76), p16 (0.68, 0.47-0.98), p27 (0.48, 0.3-0.78), E-Cadherin (0.47, 0.35-0.63), Fascin (2.19, 1.35-3.55), and Ki-67 (1.69, 1.02-2.79).
  
  
  CONCLUSIONS
  Meta-analysis has identified a number of prognostic biomarkers for resected extrahepatic cholangiocarcinoma. These markers warrant further investigation as potential therapeutic targets and validation in a prospective setting.
authors.affiliation: School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 7ZK, UK.|Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jones
authors.affiliation: Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Nicholas T E
authors.initials: NT
authors.lastname: Bird
authors.affiliation: Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Smith
authors.affiliation: School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 7ZK, UK.|Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.affiliation: Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Fenwick
authors.affiliation: Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Poston
authors.affiliation: Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, L9 7AL, UK.
authors.forename: Hassan Z
authors.initials: HZ
authors.lastname: Malik
mesh_terms: D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods* / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: COX2; CYCLIN; E-Cadherin; Fascin; GLUT1; Ki67; VEGF; cholangiocarcinoma; p16; p27