Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Background and 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. (C) 2010 Elsevier Ltd. All rights reserved.