title: Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer.
abstract: OBJECTIVE
  We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer.
  
  
  METHODS
  We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy.
  
  
  RESULTS
  Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95).
  
  
  CONCLUSIONS
  The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.
authors: University of Oxford, United Kingdom. richard.gray@ctsu.ox.ac.uk
authors: Richard G
authors: RG
authors: Gray
authors: Philip
authors: P
authors: Quirke
authors: Kelly
authors: K
authors: Handley
authors: Margarita
authors: M
authors: Lopatin
authors: Laura
authors: L
authors: Magill
authors: Frederick L
authors: FL
authors: Baehner
authors: Claire
authors: C
authors: Beaumont
authors: Kim M
authors: KM
authors: Clark-Langone
authors: Carl N
authors: CN
authors: Yoshizawa
authors: Mark
authors: M
authors: Lee
authors: Drew
authors: D
authors: Watson
authors: Steven
authors: S
authors: Shak
authors: David J
authors: DJ
authors: Kerr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods* / Q000592:standards