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

PLoS One. 2017 Sep 27;12(9):e0184937. doi: 10.1371/journal.pone.0184937. eCollection 2017.

Abstract

Background & aims: High-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.

Methodology: We 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.

Results: At 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).

Conclusions: Our results suggested that somatic KRAS mutations in polyps represent a potential molecular marker for the risk of developing advanced neoplasia.

MeSH terms

  • Colonic Polyps / complications
  • Colonic Polyps / diagnosis
  • Colonic Polyps / genetics*
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms, Second Primary / complications
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / pathology
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)

Grants and funding

This work was supported by the Instituto de Salud Carlos III (PI08/0726, INT-09/208, PI11/2630, INT-12-078, INT13-196, PI14/1386), FISABIO-ISABIAL foundation (UGP-13-221, UGP14-265), the Asociación Española contra el Cáncer (Fundación Científica GCB13131592CAST) and AIGPA, a private association that promotes research in gastrointestinal diseases in Alicante and also supported logistic aspects of the study, (this association declares no conflict of interest). Carla Guarinos and Mar Giner Calabuig received a predoctoral grant from Conselleria d’Educació de la Generalitat Valenciana (VALi+d. EXP ACIF/2010/018, ACIF/2016/002) and Eva Hernández-Illán received a grant from Instituto de Salud Carlos III (FI12/00233). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.