Introduction
We examined two genetic markers established early in colorectal tumor development, microsatellite instability (MSI) and mutation
of the KRAS proto-oncogene, to see if these genetic changes influence metastatic disease progression and survival.
Patients and methods
MSI and KRAS mutation status were assessed in 532 primary adenocarcinomas (stage I–IV) from patients treated by colon resection. Median
follow-up was 4.1 years (range 0–13.3 years) overall, 5.4 years for survivors.
Results
MSI and KRAS mutation were detected in 12 and 36% of cases, respectively. MSI was more common in early-stage disease (I, 15%; II, 21%;
III, 10%; IV, 2%; P = 0.0001). Prevalence of KRAS mutation did not vary with stage (I, 36%; II, 34%; III, 35%; IV, 40%; P = ns). Disease-specific survival was far superior for MSI tumors than for microsatellite stability (MSS) tumors (5-year survival
92 vs. 59%, P < 0.0001). KRAS mutation was a marker of poor survival (5-year survival 55 vs. 68%, P = 0.0002). Using Cox regression analysis MSI, KRAS mutation, and stage were strong independent predictors of survival in the entire patient population. A high-mortality group
with MSS/KRAS-mutant tumors was identified within the stage I and II cohort.