Current clinical practice includes testing for microsatellite instability (MSI) status, KRAS mutation status, and/or BRAF mutation status in a subset of patients with colorectal cancer (CRC) based on reported family history and stage at diagnosis. Patients with type 2 CRC had the poorest prognosis, particularly with respect to disease-specific survival (DSS). Regardless of other tumor markers, patients with MSI-high colorectal tumors had a favorable prognosis; however, this survival benefit was most evident with CIMP-positive and BRAF-mutated status (type 1 CRC). Poorer patient survival was associated with KRAS-mutated status in CRC tumors, particularly in combination with MSS/MSI-low status (type 3 CRC).
In evaluating CRC subtype classifications defined by proposed etiologic pathways, these findings demonstrate that these individual markers, in addition to CIMP status, are predictive of CRC survival—above and beyond any relationship with stage at diagnosis—particularly when considered in combination.