MSI status is associated with distinct clinicopathological features in BRAF mutation colorectal cancer: A systematic review and meta-analysis

Pathol Res Pract. 2020 Jan;216(1):152791. doi: 10.1016/j.prp.2019.152791. Epub 2019 Dec 17.


Background: Microsatellite stable (MSS) BRAF p.V600E mutation colorectal cancer (BRAF-CRC) has a poor prognosis, whereas microsatellite instability (MSI) in BRAF-CRC is associated with a favorable prognosis. Although usually considered a single clinical entity, the MSI BRAF-CRC subtype shows some distinct characteristics in comparison with the MSS BRAF-CRC subtype.

Methods: We conducted a meta-analysis to investigate the influence of clinicopathological features on MSI status in BRAF-CRC. We searched publications up to March 2019 from PubMed, Embase, and the Cochrane Library. The effect of MSI status on outcome parameters was assessed using odds ratios (ORs) with 95% confidence intervals (CIs) and fixed- or random-effects models according to the heterogeneity.

Results: After reviewing 2839 reports, 16 eligible studies including 1381 patients with BRAF-CRC met the criteria. The MSI BRAF-CRC subtype was associated with older age, female sex (OR = 1.70; 95% CI = 1.35-2.14; P < 0.00001), proximal tumor location (OR = 5.10; 95% CI = 3.70-7.03; P < 0.00001), early TNM stage (OR = 5.28; 95% CI = 3.93-7.09; P < 0.00001), and poor differentiation (OR = 2.29; 95% CI = 1.60-3.28; P < 0.00001).

Conclusions: MSI was significantly correlated with distinct favorable clinicopathological characteristics in BRAF-CRC. These results suggest that MSI status should be considered as a stratification factor for better management of the BRAF-CRC.

Keywords: BRAF p.V600E mutation; Clinicopathological features; Colorectal cancer; Microsatellite instability; Microsatellite stable.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / genetics*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation / genetics*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Young Adult


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf