DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study

摘要: Summary Background Present clinical algorithms assign adjuvant chemotherapy according to prognosis, but decisionmaking would be greatly improved if reliable predictive markers were available identify which subsets of patients benefit most from treatment. We examined molecular in preserved tissue with Dukes' B or C colon cancer randomised receive, not, fluorouracil, and assessed each marker's prognostic value. Methods Formalin-fixed paraffin-embedded paired normal tumour samples obtained 393 the UK AXIS trial postoperative portal vein infusion fluorouracil versus control. measured loss heterozygosity (LOH) microsatellite instability at four loci: P53 (17p13), D18S61 (18q22·3), D18S851 (18q21·1), DP1 (5q21). The value marker was log-rank test, by comparison treatment hazard ratios X 2 test for heterogeneity (CSH). Findings In 228 (58%) informative LOH , this significantly predictive: greater retaining than those (CSH p=0·02). Conversely, a significant outcome untreated patients. 314 (80%) least one three 17p 18q sites, whom half retained more site. effect these striking (hazard ratio 0·45, 95% CI 0·28–0·73), whereas had no (0·91; 0·56–1·48), CSH p=0·039. Interpretation Retention sites associated ability fluorouracil. These results support principle developing as factors decisions.