Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data.
METHODS
We have reviewed and pooled data from published studies to evaluate the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Thirty-one eligible studies reporting survival in 12782 patients characterised for MSI were pooled using a fixed- or random-effects model.


RESULTS
The summary odds ratio (OR) estimate for overall survival (OS) associated with MSI was 0.6 (95%CI 0.53-0.69, p<0.0001), with no evidence of heterogeneity. The effect was similar for disease-free survival (DFS) (OR=0.58, 95%CI 0.47-0.72, p<0.0001). In a subset of patients treated with 5-fluorouracil (5-FU)-based chemotherapy a significant improved prognosis was found for microsatellite stable (MSS) tumours (OR=0.52, 95%CI 0.4-0.6, p<0.0001) with no heterogeneity (p=0.53; I(2)=0%). By contrast a large heterogeneity characterised the data relative to 396 patients with MSI tumours (OR=0.69, 95%CI 0.3-1.5, p=0.1; heterogeneity: p=0.03; I(2)=58%).


CONCLUSIONS
This study confirmed the association between MSI and favourable prognosis as determined by both OS and DFS of CRC patients. A significant beneficial effect of 5-FU therapy was found for MSS tumours whilst no clear conclusion was reached for MSI tumours due to the high inter-study heterogeneity. We propose that this inconclusive result is due to the use of a single marker, such as MSI, that cannot account alone for the complexity of the mechanisms underlying 5-FU cytotoxicity. Future studies to predict response to 5-FU chemotherapy should include additional genome stability markers.
Guastadisegni
Cecilia
C
Department of Environment and Primary Prevention, Molecular Epidemiology Unit, Istituto Superiore di Sanità, Rome, Italy.
Colafranceschi
Mauro
M
Ottini
Laura
L
Dogliotti
Eugenia
E
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D053842:Microsatellite Instability; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil