Affiliations: Department of Surgical Oncology, The University of
Texas M.D. Anderson Cancer Center, Houston, Texas, USA
Note: [] Correspondence and Reprint Request: Miguel A. Rodriguez-Bigas,
MD, Department of Surgical Oncology, The University of Texas M.D. Anderson
Cancer Center, 1515 Holcombe Boulevard, Box 444, Houston, Texas 77030, USA.
Tel.: +1 713 745 4955; Fax: +1 713 745 5680; E-mail: mrodbig@mdanderson.org
Abstract: Microsatellite instability (MSI) is a well-recognized phenomenon
that is classically a feature of tumors in the hereditary non-polyposis
colorectal syndrome. Ten to 15% of sporadic colorectal cancers, however, will
have MSI. Microsatellite unstable tumors can be divided into two distinct MSI
phenotypes: MSI-high (MSI-H) and MSI-low (MSI-L). MSI sporadic colorectal
cancers with a high level of MSI (MSI-H) form a well defined group with
distinct clinicopathologic features characterized by an overall better
long-term prognosis. These sporadic MSI-H colorectal tumors most often arise
from the epigenetic silencing of the mismatch repair gene MLH1. In contrast,
MSI-L colorectal tumors have not been shown to differ in their
clinicopathologic features or in most molecular features from microsatellite
stable (MSS) tumors. Unlike MSI-H tumors, MSI-L tumors appear to arise through
the chromosomal instability carcinogenesis pathway, similar to MSS tumors. Some
groups have reported more frequent mutations in K-ras and in the methylation of
methylguanine transferase in MSI-L tumors, but others have questioned these
findings. Therefore, although the use of the MSI-L category is widespread,
there continues to be some debate as to whether a discrete MSI-L group truly
exists. Rather, it has been suggested that MSI-L tumors differ quantitatively
from MSS tumors but do not differ qualitatively. Future studies will need to
evaluate the specific mutations in non-MSI-H tumors in an attempt to
sub-classify MSI-L tumors with regard to MSS tumors so that subtle differences
between these two sub-groups can be identified.
Journal: Disease Markers, vol. 20, no. 4-5, pp. 199-206, 2004
