Do MSI-L Sporadic Colorectal Tumors Develop Through “Mild Mutator Pathway”?

Abstract

The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain. The objective of this study was to further clarify if the MSI-L phenotype could reflect a distinct pathway of tumor development with a different clinical behavior. We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors. We have found that MSI-L tumors are someway in the middle of MSI-H and MSS CRC, as they share some features with each of the other 2 subgroups: left side location, lower incidence of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L tumors show higher incidence of KRAS mutations. We believe that MSI-L tumors could be considered a distinct phenotype that develops through a "mild mutator pathway."