title: Microsatellite instability and Beta2-Microglobulin mutations as prognostic markers in colon cancer: results of the FOGT-4 trial.
abstract: BACKGROUND
  High-level microsatellite instability (MSI-H) has been reported as a prognostic marker in colon cancer. We here analysed the prognostic significance of MSI and mutations of the Beta2-Microglobulin (B2M) gene, which occur in about 30% of MSI-H colon cancer, in the cohort of the prospective FOGT-4 (Forschungsruppe Onkologie Gastrointestinale Tumoren, FOGT) trial.
  
  
  METHODS
  Microsatellite instability status was determined using standard protocols (NCI/ICG-HNPCC panel and CAT25) in 223 colon cancer lesions. Beta2-Microglobulin mutation status was evaluated by exon-wise sequencing in all MSI-H lesions.
  
  
  RESULTS
  Patients with MSI-H (n=34) colon cancer presented with a significantly lower risk of relapse after 12 months of follow-up compared with MSS (n=189) colon cancer patients (5 year time to relapse: MSI-H 0.82 vs MSS 0.66, P=0.03). No significant difference in overall survival was detected. Beta2-Microglobulin mutations were identified in 10 (29.4%) out of 34 MSI-H colon cancers and were associated with a complete absence of disease relapse or tumour-related death events (P=0.09).
  
  
  CONCLUSIONS
  The risk of late disease relapse was significantly lower in patients with MSI-H compared with MSS colon cancer. Moreover, B2M mutations may contribute to the favourable outcome of MSI-H colon cancer patients and should therefore be evaluated as a potential prognostic marker in future clinical trials.
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg 69120, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Tikidzhieva
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.forename: S
authors.initials: S
authors.lastname: Michel
authors.forename: A
authors.initials: A
authors.lastname: Formentini
authors.forename: K-H
authors.initials: KH
authors.lastname: Link
authors.forename: W
authors.initials: W
authors.lastname: Dippold
authors.forename: M
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: M
authors.initials: M
authors.lastname: Kornmann
authors.forename: M
authors.initials: M
authors.lastname: Kloor
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D001613:beta 2-Microglobulin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin