title: Validation of the 12-gene colon cancer recurrence score as a predictor of recurrence risk in stage II and III rectal cancer patients.
abstract: BACKGROUND
  The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial.
  
  
  METHODS
  RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided.
  
  
  RESULTS
  Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients).
  
  
  CONCLUSIONS
  The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers.
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Marlies S
authors.initials: MS
authors.lastname: Reimers
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Margarita
authors.initials: M
authors.lastname: Lopatin
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Haluk
authors.initials: H
authors.lastname: Tezcan
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Kim
authors.initials: K
authors.lastname: Clark-Langone
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Liefers
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS).
authors.forename: Steve
authors.initials: S
authors.lastname: Shak
authors.affiliation: Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS). c.j.h.van_de_Velde@lumc.nl.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000235:genetics*; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D060888:Real-Time Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology*