Purpose: The aim of this study was to investigate the prognostic value of the combination of microsatellite instability (MSI) and BRAF  V600E mutation in colorectal cancer (CRC).
Materials and methods: We compare the prognosis difference among CRC patients with four subtypes according to MSI and BRAF  mutation, ie, microsatellite stable/BRAF  wild type (MSS/BRAF  wt), MSS/BRAF  mutation (MSS/BRAF  mut), MSI/BRAF  wt, and MSI/BRAF  mut, by pooling the previous related reports and public available data sets till December 2017 for the first time.
Results: Twenty-seven independent studies comprising 24,067 CRC patients were included. Meta-analysis suggested that, compared with MSS/BRAF  wt subtype, MSS/BRAF  mut was associated with shorter overall survival (OS) (N=25, HR = 2.018, 95% CI = 1.706–2.388, P =2.220E-16), while there was a trend of association of MSI/BRAF  mut with OS (N=13, HR = 1.324, 95% CI = 0.938–1.868, P =1.096E-01) and no association of MSI/BRAF  wt with OS (N=17, HR = 0.996, 95% CI = 0.801–1.240, P =9.761E-01). Compared with MSI/BRAF  wt subtype, MSI/BRAF  mut was a poor factor for OS (N=22, HR = 1.470, 95% CI = 1.243–1.740, P =7.122E-06). Compared with MSS/BRAF  mut subtype, both MSI/BRAF  wt (N=11, HR = 0.560, 95% CI = 0.433–0.725, P =1.034E-05) and MSI/BRAF  mut (N=16, HR = 0.741, 95% CI = 0.567–0.968, P =2.781E-02) were favorable for OS. Subgroup analysis revealed similar results in all subgroups except the subgroup of stage IV cancer, in which MSI showed poor effects on OS in BRAF  wild-type patients (N=6, HR = 1.493, 95% CI = 1.187–1.879, P =6.262E-04) but not in BRAF -mutated patients (N=5, HR = 1.143, 95% CI = 0.789–1.655, P =4.839E-01). Meta-analysis regression and test of interaction revealed no interaction of MSI with BRAF  mutation when evaluating the associations of MSI/BRAF  mutation subtypes with OS in CRC.
Conclusion: Among the four subtypes according to MSI and BRAF  mutation, MSS/BRAF  mut was a poor prognostic factor, while MSS/BRAF  wt and MSI/BRAF  wt were comparable and favorable and MSI/BRAF  mut was moderate in CRC. The combination of MSI/BRAF  mutations could facilitate the planning of individualized treatment strategies and prognosis improvement in CRC.
Keywords: meta-analysis, microsatellite instability, colorectal cancer, BRAF  mutation, prognosis