BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status

J Korean Med Sci. 2017 Jan;32(1):38-46. doi: 10.3346/jkms.2017.32.1.38.

Abstract

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.

Keywords: BRAF V600E; Clinicopathological Feature; Colorectal Cancer; Microsatellite Instability.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • ErbB Receptors / metabolism
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Immunochemistry
  • Kaplan-Meier Estimate
  • Leucovorin / therapeutic use
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Organoplatinum Compounds / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Organoplatinum Compounds
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins B-raf
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol