High frequency of low-level microsatellite instability in early colorectalcancer

Molecular events in early colorectal cancers (CRCs) have not been well eluc idated because of the low incidence of early CRCs in clinical practice. The refore, we studied 104 sporadic early CRCs with invasion limited to submuco sa compared with 116 advanced CRCs. Loss of heterozygosity as well as micro satellite instability (MSI) status was examined. A significantly high frequ ency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs , samples with MSI-L phenotype differed from microsatellite stable (MSS) ph enotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L i s a frequent genetic event in early CRCs and may be a novel pathway in colo rectal carcinogenesis distinct from both MSI-H and MSS.