KRAS and BRAF somatic mutations in colonic polyps and the risk of metachronous neoplasia

Abstract

Background & aimsHigh-risk features of colonic polyps are based on size, number, and pathologic characteristics. Surveillance colonoscopy is often recommended according to these findings. This study aimed to determine whether the molecular characteristics of polyps might provide information about the risk of metachronous advanced neoplasia.MethodologyWe retrospectively included 308 patients with colonic polyps. A total of 995 polyps were collected and tested for somatic BRAF and KRAS mutations. Patients were classified into 3 subgroups, based on the polyp mutational profile at baseline, as follows: non-mutated polyps (Wild-type), at least one BRAF-mutated polyp, or at least one KRAS-mutated polyp. At surveillance, advanced adenomas were defined as adenomas ≥ 10 mm and/or with high grade dysplasia or a villous component. In contrast, advanced serrated polyps were defined as serrated polyps ≥ 10 mm in any location, located proximal to the splenic flexure with any size or with dysplasia.ResultsAt baseline, 289 patients could be classified as wild-type (62.3%), BRAF mutated (14.9%), or KRAS mutated (22.8%). In the univariate analysis, KRAS mutations were associated with the development of metachronous advanced polyps (OR: 2.36, 95% CI: 1.22–4.58; P = 0.011), and specifically, advanced adenomas (OR: 2.42, 95% CI: 1.13–5.21; P = 0.023). The multivariate analysis, adjusted for age and sex, also showed associations with the development of metachronous advanced polyps (OR: 2.27, 95% CI: 1.15–4.46) and advanced adenomas (OR: 2.23, 95% CI: 1.02–4.85).ConclusionsOur results suggested that somatic KRAS mutations in polyps represent a potential molecular marker for the risk of developing advanced neoplasia.

Clinicopathological factors associated with BRAF‐V600E mutation in colorectal serrated adenomas

“…Regarding macroscopic morphology, an association between a flat appearance and BRAF mutations has been reported . Such an association would be consistent with the higher BRAF mutation rates in SSA (which is sessile by definition) than TSA (which is typically pedunculated) .…”

Identifying Modules of Cooperating Cancer Drivers

“…From a biological perspective, cooccurrence of driver alterations clearly does occur [17,18,19,20], and appears to be a requirement for carcinogenesis, as evidenced by the insufficiency of BRAF and RAS hotspot mutations to transform benign colon polyps and nevi into invasive carcinoma [21,22]. However, statistical approaches to identifying cooccurrence have given mixed results.…”

Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions

“…Previous studies have investigated the role of molecular markers in polyps for predicting the development of metachronous lesions, especially advanced adenomas, revealing an increased MACL risk in patients with KRAS-mutated polyps at baseline [ 5 ]. Concerning serrated lesions, a recent study has found no association between BRAF mutations or CIMP status in polyps at baseline and metachronous advanced lesions [ 11 ].…”

“…To date, few studies have investigated the relationship between molecular markers and risk of developing metachronous neoplasia at follow-up. Some prior studies demonstrate that somatic mutation in KRAS ( K irsten RA t S arcoma virus) gene may predict metachronous advanced colorectal lesions (MACLs) during colonoscopic surveillance [ 5 ]. Additionally, studies applying the consensus molecular subtypes (CMSs) of CRC to polyps have indicated that certain genetic anomalies may be markers of future CRC risk [ 6 , 7 ].…”