title: Molecular prognostic markers in resectable colorectal liver metastases: a systematic review.
abstract: BACKGROUND
  Determination of prognosis in patients with resectable colorectal liver metastases (CLM) is desirable in order to improve case selection for surgery and tailor adjuvant treatment according to individual recurrence risk. Conventional clinicopathological factors lack the sensitivity to accurately achieve this goal. Consideration of tumour biology and the identification of molecular prognostic markers may allow more accurate risk stratification.
  
  
  METHODS
  This systematic review examines evidence from published manuscripts looking at molecular markers in resectable colorectal liver metastases and their correlation with disease recurrence and survival following hepatectomy.
  
  
  RESULTS
  Studies have yielded promising results in the search for prognostic molecular markers of CLM. Molecular biomarkers from varied aspects of tumour biology have been examined and a number of these, including proliferation indices, telomerase, thymidylate synthase, microvessel density and thrombospondin-1 appear to have prognostic utility in this context. Validation of other markers, notably p53, has been limited by a failure of methodologies to account for their biological complexity.
  
  
  CONCLUSIONS
  A biomarker-based approach may yield significant benefits through informed treatment of resectable metastatic colorectal malignancy. Standardised retrospective analyses are necessary to confirm preliminary findings and identify existing and novel markers for inclusion into prospective studies. Assessment and verification of multiple molecular markers in this manner may allow molecular profiling of metastases and tailoring of therapy according to the biological aggressiveness of individual tumours. The advent of genomic- and proteomic-based technologies will allow the simultaneous analysis of multiple molecular markers and the derivation of disease profiles associated with disease recurrence and poor survival.
authors.affiliation: Department of Biochemistry, Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom. cpn3@le.ac.uk
authors.forename: C P
authors.initials: CP
authors.lastname: Neal
authors.forename: G
authors.initials: G
authors.lastname: Garcea
authors.forename: H
authors.initials: H
authors.lastname: Doucas
authors.forename: M M
authors.initials: MM
authors.lastname: Manson
authors.forename: C D
authors.initials: CD
authors.lastname: Sutton
authors.forename: A R
authors.initials: AR
authors.lastname: Dennison
authors.forename: D P
authors.initials: DP
authors.lastname: Berry
mesh_terms: D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000556:secondary*; D009389:Neovascularization, Pathologic / Q000175:diagnosis; D009857:Oncogenes / Q000235:genetics; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D013940:Thymidylate Synthase; D019098:Telomerase