Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps

Background: The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Aim: Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. Methods: A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10 mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3 years ± 6 months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10 mm. High-grade dysplasia or villous component, serrated polyps ≥10 mm or with dysplasia or CRC. Results: At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20 mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02–1.09; p < 0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96–7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48–4.34; p < 0.01) were independently associated with the development of advanced lesions at surveillance. Conclusions: Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.