Molecular heterogeneity of colorectal cancer: Implications for cancer control.

Colorectal cancer (CRC) is a multi-pathway disease. A molecular approach to the classification of CRC utilises: (1) the type of genetic instability, specifically microsatellite instability (MSI) versus stable (MSS), and (2) the presence of DNA methylation or the CpG island methylator phenotype (CIMP). The MSS/CIMP-neg subset evolves through the classical adenoma-carcinoma sequence while the MSI/CIMP-pos and MSS/CIMP-pos subsets evolve through the recently recognised 'serrated pathway'. This review will show that the existence of two or more independent pathways to CRC is relevant to cancer prevention. In particular, new strategies for detecting and managing sessile serrated polyps will need to be developed and evaluated.