title: Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group.
abstract: OBJECTIVE
  Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently.
  
  
  METHODS
  In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed.
  
  
  RESULTS
  The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients (p = 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival.
  
  
  CONCLUSIONS
  MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort.
authors.affiliation: Institute of Physiology, University Hospital Essen, Essen, Germany.
authors.forename: C I
authors.initials: CI
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Schulmann
authors.forename: A
authors.initials: A
authors.lastname: Reinacher-Schick
authors.forename: N
authors.initials: N
authors.lastname: Andre
authors.forename: D
authors.initials: D
authors.lastname: Arnold
authors.forename: A
authors.initials: A
authors.lastname: Tannapfel
authors.forename: H
authors.initials: H
authors.lastname: Arkenau
authors.forename: S A
authors.initials: SA
authors.lastname: Hahn
authors.forename: S H-J
authors.initials: SH
authors.lastname: Schmoll
authors.forename: R
authors.initials: R
authors.lastname: Porschen
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.forename: U
authors.initials: U
authors.lastname: Graeven
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D004273:DNA, Neoplasm / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D053842:Microsatellite Instability / Q000187:drug effects*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007166:Immunosuppressive Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil