MSI Clinical Results

Kaplan–Meier Estimates of Overall Survival among Patients with Stage II or Stage III Colon Cancer According to the Microsatellite-Instability Status of the Tumor.

• In the absence of adjuvant chemotherapy, the patients with tumors displaying high-frequency microsatellite instability had significantly longer overall survival than patients with tumors exhibiting microsatellite stability or low-frequency microsatellite instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004)(Panel A).
• When the analysis was limited to the group receiving adjuvant chemotherapy, patients with tumors exhibiting high-frequency microsatellite instability did not have a significant increase in overall survival as compared with patients with tumors exhibiting microsatellite stability or low-frequency microsatellite instability (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80)(Panel B).
• The analysis included data for eight years from the date of randomization.

N Engl J Med 2003;349:247-57.
 

•  Most hypermethylation, not mutation
   

• MMR cells unable to bind 5-FU modified DNA

• More sensitive to irinotecan
• Not resistant to oxaliplatin

• dMMR validated as prognostic marker in untreated patients.
• No suggestion of benefit from 5-FU–based treatment in patients with dMMR.
• Significant OS decrement to 5-FU–based treatment in patients with Stage II disease.