title: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. We tested the hypothesis that colorectal cancers arising from the microsatellite-instability pathway have distinctive clinical attributes that affect clinical outcome.
  
  
  METHODS
  We tested specimens of colorectal cancer from a population-based series of 607 patients (50 years of age or younger at diagnosis) for microsatellite instability. We compared the clinical features and survival of patients who had colorectal cancer characterized by high-frequency microsatellite instability with these characteristics in patients who had colorectal cancers with microsatellite stability.
  
  
  RESULTS
  We found high-frequency microsatellite instability in 17 percent of the colorectal cancers in 607 patients, and in a multivariate analysis, microsatellite instability was associated with a significant survival advantage independently of all standard prognostic factors, including tumor stage (hazard ratio, 0.42; 95 percent confidence interval, 0.27 to 0.67; P< 0.001). Furthermore, regardless of the depth of tumor invasion, colorectal cancers with high-frequency microsatellite instability had a decreased likelihood of metastasizing to regional lymph nodes (odds ratio, 0.33; 95 percent confidence interval, 0.21 to 0.53; P< 0.001) or distant organs (odds ratio, 0.49; 95 percent confidence interval, 0.27 to 0.89; P=0.02).
  
  
  CONCLUSIONS
  High-frequency microsatellite instability in colorectal cancer is independently predictive of a relatively favorable outcome and, in addition, reduces the likelihood of metastases.
authors.affiliation: Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Gryfe
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: E T
authors.initials: ET
authors.lastname: Hsieh
authors.forename: M D
authors.initials: MD
authors.lastname: Aronson
authors.forename: E J
authors.initials: EJ
authors.lastname: Holowaty
authors.forename: S B
authors.initials: SB
authors.lastname: Bull
authors.forename: M
authors.initials: M
authors.lastname: Redston
authors.forename: S
authors.initials: S
authors.lastname: Gallinger
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis