Molecular profiling of sporadic colorectal tumors by microsatellite analysis

To investigate the prognostic value of multiple genetic alterations, indivi dual molecular tumor profiles were established in 79 sporadic colorectal ca rcinomas (41 stage II and 38 stage III). Tumors were analyzed for allelic l oss (LOH) and genetic instability (MSI) using 14 microsatellites intragenic to or associated with tumor suppressor or DNA mismatch repair genes. Molec ular profiling identified tumors with LOH at multiple loci without microsat ellite instability (MSS), tumors with high levels of LOH and low level micr osatellite marker instability (MSI-L), and tumors with high levels of MSI ( MSI-H), but rare LOH. K-ras mutations occured more frequently in MSS/MSI-L carcinomas (26%) than in MSI-H colorectal tumors (10%), the latter showing a high frequency of TGF beta type II frameshift mutations (82%). Correlatio n of molecular and clinical data revealed a better prognosis for stage III tumor patients displaying 5q12 loss rather than retention of heterozygosity . Thus, molecular profiling allows the identification of new prognostic mar kers and might facilitate the stratification of colorectal cancer patients.