Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer

Background: Colorectal cancer can arise through two distinct mutational pat hways: microsatellite instability or chromosomal instability. We tested the hypothesis that colorectal cancers arising from the microsatellite-instabi lity pathway have distinctive clinical attributes that affect clinical outc ome. Methods: We tested specimens of colorectal cancer from a population-based s eries of 607 patients (50 years of age or younger at diagnosis) for microsa tellite instability. We compared the clinical features and survival of pati ents who had colorectal cancer characterized by high-frequency microsatelli te instability with these characteristics in patients who had colorectal ca ncers with microsatellite stability. Results: We found high-frequency microsatellite instability in 17 percent o f the colorectal cancers in 607 patients, and in a multivariate analysis, m icrosatellite instability was associated with a significant survival advant age independently of all standard prognostic factors, including tumor stage (hazard ratio, 0.42; 95 percent confidence interval, 0.27 to 0.67; P<0.001 ). Furthermore, regardless of the depth of tumor invasion, colorectal cance rs with high-frequency microsatellite instability had a decreased likelihoo d of metastasizing to regional lymph nodes (odds ratio, 0.33; 95 percent co nfidence interval, 0.21 to 0.53; P<0.001) or distant organs (odds ratio, 0. 49; 95 percent confidence interval, 0.27 to 0.89; P=0.02). Conclusions: High-frequency microsatellite instability in colorectal cancer is independently predictive of a relatively favorable outcome and, in addi tion, reduces the likelihood of metastases. (N Engl J Med 2000;342:69-77.) (C) 2000, Massachusetts Medical Society.