title: Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study.
abstract: OBJECTIVE
  The role of high-degree microsatellite instability (MSI-H) as a marker to predict benefit from adjuvant chemotherapy remains unclear.
  
  
  METHODS
  To help define its impact, we conducted an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) patients who were randomly assigned to a surgery-alone group (untreated cohort) and patients assigned to an adjuvant fluorouracil (FU) -treated group (treated cohort). MSI-H and other potential markers were assessed (TGF-BRII, p53, thymidylate synthase, and Ki67).
  
  
  RESULTS
  In all, 98 (18.1%) of 542 patients exhibited MSI-H, and there was a strong inverse relationship between MSI-H and mutant p53 status (P < .001). The prognostic analyses showed increased recurrence-free survival (RFS) for MSI-H patients versus MSS/MSI-L patients (P = .10), but showed no difference in overall survival (OS; P = .67). There was a potential interaction between MSI-H and mutant p53 in terms of improved RFS (P = .03). In the predictive marker analysis, we observed no interaction between MSI status and treatment for either RFS (P = .68) or OS (P = .62). Hazard ratios (HR) for RFS for MSI-H versus MSS/MSI-L patients were 0.77 (95% CI, 0.40 to 1.48) in the untreated-patients group and 0.60 (95% CI, 0.30 to 1.19) in the treated-patients group. HRs for OS were 0.82 (95% CI, 0.44 to 1.51) and 1.02 (95% CI, 0.56 to 1.85) for the respective groups. There was a trend toward improved RFS in patients with MSI-H and mutant p53.
  
  
  CONCLUSIONS
  These results do not support the use of MSI-H as a predictive marker of chemotherapy benefit.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project (NSABP) Operations and Biostatistical Centers, Mayo Clinic, Jacksonville, FL 32224, USA. kim.george@mayo.edu
authors.forename: George P
authors.initials: GP
authors.lastname: Kim
authors.forename: Linda H
authors.initials: LH
authors.lastname: Colangelo
authors.forename: H Samuel
authors.initials: HS
authors.lastname: Wieand
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Ilan R
authors.initials: IR
authors.lastname: Kirsch
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Allegra
mesh_terms: D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D016158:Genes, p53; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics
chemical_list: D019394:Ki-67 Antigen; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II