title: Molecular profiles and clinical outcome of stage UICC II colon cancer patients.
abstract: OBJECTIVE
  Published multigene classifiers suggesting outcome prediction for patients with stage UICC II colon cancer have not been translated into a clinical application so far. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable their reconstruction in routine diagnostic specimens.
  
  
  METHODS
  Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of previously published prognostic classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by "nearest shrunken centroids" with cross-validation. Previously published gene signatures were applied to our data set using "global tests" and leave-one-out cross-validation
  
  
  RESULTS
  Correlation of protein expression with clinical outcome failed to separate patients with disease-free follow-up (group DF) and relapse (group R). Although gene expression profiling allowed the identification of differentially expressed genes ("DF" vs. "R"), a stable classification/prognosis signature was not discernable. Furthermore, the application of previously published gene signatures to our data was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse with established clinical and pathological parameters including microsatellite status (multivariate analysis).
  
  
  CONCLUSIONS
  Our protein and gene expression analyses do not support application of molecular classifiers for prediction of clinical outcome in current routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.
authors.affiliation: Department of General, Vascular and Thoracic Surgery, Charité University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. joern.groene@charite.de
authors.forename: Jörn
authors.initials: J
authors.lastname: Gröne
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Vindi
authors.initials: V
authors.lastname: Jurinovic
authors.forename: Manuela
authors.initials: M
authors.lastname: Hummel
authors.forename: Henrik
authors.initials: H
authors.lastname: Seidel
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leder
authors.forename: Georg
authors.initials: G
authors.lastname: Beckmann
authors.forename: Anette
authors.initials: A
authors.lastname: Sommer
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Heinz-Johannes
authors.initials: HJ
authors.lastname: Buhr
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins