Microsatellite instability and prognosis of colorectal cancer

Purpose: Many studies have evaluated the role of high levels of microsatellite instability (MSI) asa prognostic marker and predictor of the response to chemotherapy in colorectal cancer (CRC);however, the results are not conclusive.The aim of this study was to analyze the prognostic significanceof high levels of MSI (MSI-H) in CRC patients in relation to fluorouracil-based chemotherapy.ExperimentalDesign: In three different institutions,1,263 patientswithCRCwere tested for thepresence of MSI, and CRC-specific survival was then analyzed in relation toMSI status, chemotherapy,and other clinical and pathologic variables.Results:Two hundred and fifty-six tumorswereMSI-H(20.3%): theseweremore frequently at aless advanced stage, right-sided, poorly differentiated, withmucinous phenotype, and expansivegrowth pattern than microsatellite stable carcinomas. Univariate and multivariate analyses of5-year ^ specific survival revealed stage, tumor location, grade of differentiation, MSI, gender,and age as significant prognostic factors.The prognostic advantage of MSI tumors was particularlyevident in stages II and III in which chemotherapy did not significantly affect the survival ofMSI-H patients. Finally, we analyzed survival inMSI-H patients in relation to the presence ofmismatchrepair gene mutations. MSI-H patients with hereditary non ^ polyposis colorectal cancershowed a better prognosis as compared with sporadic MSI-H; however, in multivariate analysis,this difference disappeared.Conclusions:The type of genomic instability could influence the prognosis of CRC, in particularin stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival amongMSI-Hpatients.The survival benefit for patientswithhereditary non ^ polyposis colorectal canceris mainly determined by younger age and less advanced stage as comparedwith sporadicMSI-Hcounterpart.