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

Abstract

Background: 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. Methods: We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors. Results: 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. Conclusion: We believe that MSI-L tumors could be considered a distinct phenotype that develops through a “mild mutator pathway.”