title: Prognostic and predictive relevance of microsatellite instability in colorectal cancer.
abstract: Microsatellite instability (MSI) is the phenotypic hallmark of a deficient DNA mismatch-repair system, observed in 10-20% of sporadic colorectal cancers (CRC). Since the prognostic and predictive value of this genetic alteration has been assessed mainly in non-randomised, uncontrolled studies, we investigated the potential of MSI to predict patient survival and response to adjuvant chemotherapy in tumour specimens from a randomised trial of the Swiss Group for Clinical Cancer Research (SAKK) that tested the value of 5-fluorouracil/mitomycin adjuvant chemotherapy. MSI status was determined in matched normal and tumour tissue samples from 160 patients using a panel of 9 microsatellite markers. There was no correlation between high frequency MSI (MSI-H) and overall (OS) or disease-free survival (DFS) in the untreated control group of patients (HR=1.13, p=0.80; and HR=0.89, p=0.81, respectively). Furthermore, MSI-H phenotype did not predict for a larger benefit of adjuvant chemotherapy on OS or DFS (HR=0.49, p=0.41; HR=0.49, p=0.41, respectively), making a potential value of this molecular marker as a predictive factor in CRC unlikely. Our data do not confirm the prognostic relevance of MSI-H status in colorectal cancer patients found in some other studies. In addition, microsatellite instability did not correlate with the extent of chemotherapy benefit, although we observed a statistically non-significant favourable impact of 5-FU-based treatment in the MSI-H group compared to MSI-L/MSS patients. Larger prospective randomised trials are required to conclusively establish a potential clinical significance of MSI in colorectal cancer.
authors.affiliation: Department of Research, University Hospital of Basel, CH-4031, Switzerland.
authors.forename: Iana
authors.initials: I
authors.lastname: Storojeva
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Boulay
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Ballabeni
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Urban
authors.initials: U
authors.lastname: Laffer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mild
authors.forename: Richard
authors.initials: R
authors.lastname: Herrmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D015999:Multivariate Analysis; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012196:Review Literature as Topic; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D016685:Mitomycin; D005472:Fluorouracil