Microsatellite instabilityDNA testing in routinely processed colorectal carcinomas: correlation with clinicopathologic and survival data in 340 consecutive cases

Background. Colorectal cancer (CRC) is characterized by a multistep progression of genetic errors. Two different pathways are identified, that of chromosomal instability (CIN) and the microsatellite instability (MSI) pathway. Widespread microsatellite instability (MSI high, MSI-H phenotype) is present in 10-20% of sporadic colorectal cancers and characterizes patients with the inherited Lynch syndrome (Hereditary non polyposis colorectal cancer, HNPCC). MSI-H tumors have distinctive pathologic features, and are believed to behave less aggressively when compared with tumors that lack microsatellite instability (microsatellite stable, MSS) or that show instability at a few loci (microsatellite low, MSI-L phenotype). Methods. We studied 340 consecutive CRCs for MSI using multiplexed polymerase chain reaction (PCR) for 12 microsatellite markers followed by capillary electrophoresis with a DNA sequencer. DNA was extracted from routinely processed formalin-fixed tissue. All surgical specimens underwent routine histopathological analysis for grading and staging. Tumors were considered MSI-H when 4 or more of the 12 loci were mutated , MSI-L when 1-3 loci were mutated and MSS when no mutations were identified. Results. 40 CRCs were MSI-H (11,5%), 45 CRCs were MSI-L (13,5%) and 255 CRCs were MSS (75%). Correlation with clinicopathologic features confirms previous findings that show how MSI-H CRCs are more common in the right colon, display poorly differentiated histologic features and show prominent lymphocytic infiltration when compared with MSI-L and MSS tumors. Survival analysis after a median follow-up of 45 months shows that MSI-H tumors have a better prognosis in patients with stage 1 and 2 disease, but the prognosis is considerably worse for stage 3 and 4 disease (p