Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers

Background: Microsatellite instability (MSI) and allelic imbalance involvin g chromosome arms 5q, 8p, 17p, and 18q are genetic alterations commonly fou nd in colorectal cancer. We investigated whether the presence or absence of these genetic alterations would allow stratification of patients with Astl er-Coller stage B2 or C colorectal cancer into favorable and unfavorable pr ognostic groups. Methods: Tumors from 508 patients were evaluated for MSI a nd allelic imbalance by use of 11 microsatellite markers located on chromos ome arms 5q, 8p, 15q, 17p, and 18q, Genetic alterations involving each of t hese markers were examined for associations with survival and disease recur rence. All P values are two-sided. Results: In univariate analyses, high MS I (MSI-H), i.e., MSI at 30% or more of the loci examined, was associated wi th improved survival (P = .02) and time to recurrence (P = .01), The group of patients whose tumors exhibited allelic imbalance at chromosome 8p had d ecreased survival (P = .02) and time to recurrence (P = .004), No statistic ally significant associations with survival or time to recurrence were obse rved for markers on chromosome arms 5q, 15q, 17p,Or 18q, In multivariate an alyses, MSI-H was an independent predictor of improved survival (hazard rat io [HP] = 0.51; 95% confidence interval [CI] = 0.31-0.82; P = .006) and tim e to recurrence (HR = 0.42; 95% CI = 0.24-0.74; P = .003), and 8p allelic i mbalance was an independent predictor of decreased survival (HR = 1.89; 95% CI = 1.25-2.83; P = .002) and time to recurrence (HR = 2.07; 95% CI = 1.32 -3.25; P = .002), Conclusions: Patients whose tumors exhibited MSI-H had a favorable prognosis, whereas those with 8p allelic imbalance had a poor pro gnosis; both alterations served as independent prognostic factors, To our k nowledge, this is the first report of an association between 8p allelic imb alance and survival in patients with colorectal cancer.