Purpose : Colon cancer shows various genetic alterations in its development and progression. Recently, microsatellite instability (MSI) has been related to a novel mechanism of carcinogenesis, and might be a useful prognostic factor in several gastrointestinal malignancies. The loss of heterozygosity (LOH) is known to be related with the allelic loss of various tumor suppressor genes, however, MSI, which has been found to result from an erroneous DNA mismatch repair system, has been known to be involved in the carcinogenesis of hereditary non-polyposis colon cancers and some aspects of sporadic colorectal cancers. In this study, the status of MSI was examined in sporadic colon cancers, and its correlation with various clinico-pathological parameters investigated.
Methods : Fifty sporadic coloretal cancers, treated by surgery alone, were analyzed for the presence of MSI using microsatellite markers, and tumor and normal DNA, obtained from formalin-fixed paraffin-embedded archival tissues. MSIs were examined at the BAT25, BAT26, D2S123, D5S346 and D17S250 loci, as recommended in the 1997 NIH International Workshop on Microsatellite Instabilities and RER phenotypes.
Results : MSI was detected in 11 cases (22%), and was more frequently detected in the non-metastatic adenocarcinoma and Astler-Coller stages A+B1+C1 groups than in the metastatic and B2+C2+D groups. Also, there were no metastatic cases in the MSI-high group, where more than 3 loci had MSI. LOH was detected in three of the recommended markers, and was observed in 17 cases (34%). LOH was more highly detected in the metastatic and B2+C2+D groups, but there was no correlation with the clinico-pathological parameters. However, no LOH-positive cases were found in the MSI-positive group.
Conclusion : These results suggest that MSI may be partially involved in colorectal carcinogenesis and the metastasis mechanism. Also, the clinical use of the MSI status may help in determining the prognosis of coloretal cancer patients
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