Abstract

Colorectal cancer (CRC) has been assumed for many years to be a homogenous condition with the vast majority developing within preexisting-adenomas. However, over the last two-decades, it has become clear that CRC evolves through multiple pathways at the genetic and the epigenetic level. Each of these processes is associated with a unique genetic or epigenetic signature identifiable in the tumor cells. The pathway may be defined on the basis of three molecular features: 1) chromosomal instability (CIN), 2) microsatellite instability (MSI), and 3) CpG island methylator phenotype (CIMP). Those molecular pathways are determined at an early evolutionary stage and are fully established within early cancer. Recently, five subgroups were outlined by using morphological findings and associated molecular changes: type 1 (CIN-stable/ MSI-H/CIMP-H), type 2 (CIN-stable/MSI-L or MSS/ CIMP-H), type 3 (CIN-unstable/MSI-L or MSS/CIMP-L), type 4 (CIN-instable/MSS/CIMP-neg), and type 5 (CIN- stable/MSI-H/CIMP-neg). This approach to the classification of CRC should accelerate understanding of causation and will have an impact on clinical management in the areas of both prevention and treatment.

• Keywords: Colorectal cancer;Genetic;Epigenetic;Pathway;Classification