Key characteristics of the three major CRC pathways.
| ||Chromosomal instability (CIN)||Microsatellite instability (MSI)||CpG island methylation (CIMP)|
|Prevalence||80–85%||15–20%||Up to 20%|
|Molecular Events||Characterized by aneuploidy, inactivation of APC/b-catenin, clonal accumulation of genetic alterations in oncogenes and tumor suppressor genes, and allelic losses and gains [49–51] ||Mutations/epimutations in the MMR genes result in extensive insertions and/or deletions in microsatellites||Hypermethylation of multiple promoter CpG island loci, such as hMLH1 [9, 52]. BRAF mutations |
|Clinical features||Associated with poor prognosis [54, 55]||Associated with proximal tumor location, lower staging, high grade differentiation, and abundance of tumor infiltrating lymphocytes [56, 57]||Correlates with proximal tumor location, higher prevalence in females, and BRAF mutations [58–61] |