Abstract

BackgroundWe systematically reviewed the evidence for the interaction of microsatellite instability status (MSI) and treatment with 5FU in colorectal cancer to determine how well MSI status predicts health outcomes in patients undergoing 5FU-based chemotherapy.MethodsWe conducted a search of four electronic databases through June 2013. We considered studies that included both colorectal cancer patients treated with 5FU-based chemotherapy and untreated patients with survival outcomes presented by MSI status.ResultsWe identified 16 studies for qualitative analysis (9,212 patients) with 14 studies eligible for meta-analysis. The microsatellite stable (MSS) group showed an effect of 5FU treatment on disease-free survival (HR of 0.62 [95% CI: 0.54, 0.71]) and overall survival (HR of 0.65 [95% CI: 0.54, 0.79]), indicating that MSS patients who received 5FU treatment had longer survival than MSS patients who were untreated. The effect of 5FU treatment was not statistically significant for microsatellite high (MSI-H) patients for disease-free survival (HR of 0.84 [95% CI: 0.53, 1.32]) or overall survival (HR 0.66 [95% CI: 0.43, 1.03]). However, the summarized point estimates of the effects of 5FU treatment for the MSS and MSI-H groups were not different at a statistically significant level.ConclusionsOur analyses indicate that treatment with 5FU-based chemotherapy improves disease-free and overall survival in CRC patients, but that there is no difference in the effect of treatment based on MSI status. Therefore, the use of MSI status to guide treatment decisions about the use of 5FU treatment for CRC has no significant benefits for patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1093-4) contains supplementary material, which is available to authorized users.

Highlights

  • We systematically reviewed the evidence for the interaction of microsatellite instability status (MSI) and treatment with 5FU in colorectal cancer to determine how well MSI status predicts health outcomes in patients undergoing 5FU-based chemotherapy

  • Eligibility criteria We considered studies that included both Colorectal cancer (CRC) patients treated with 5FU-based chemotherapy and untreated patients with survival outcomes presented by MSI status

  • We conclude that the results of this meta-analysis do not support the use of MSI status for the direct benefit of the patient in guiding decisions about the use of 5FU treatment for CRC

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Summary

Introduction

We systematically reviewed the evidence for the interaction of microsatellite instability status (MSI) and treatment with 5FU in colorectal cancer to determine how well MSI status predicts health outcomes in patients undergoing 5FU-based chemotherapy. About 15% of CRC tumors develop via a pathway characterized by defective function of the DNA mismatch repair (MMR) system. MMR deficiency most commonly occurs through epigenetic inactivation of the MLH1 gene in sporadic CRCs, but can occur through inherited mutations in any one of four genes (i.e., MLH1, MSH2, MSH6, and PMS2). Tumors with MMR deficiency exhibit a high frequency of microsatellite instability (MSI-H) because these regions of the genome are unstable and susceptible to errors that do not get corrected because of the defective MMR system [2]. For determining MSI status, the National Cancer Institute (NCI) recommends a microsatellite panel (NCI panel) consisting of two mononucleotide repeats (BAT26 and A4725) and three dinucleotide repeats (D5S346, D2S123, and D17S250). Tumor MMR status is determined by immunohistochemical (IHC) analysis of the protein products of genes

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