title: Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.
abstract: BACKGROUND
  It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC.
  
  
  METHODS
  By using prospective clinical data and molecular analyses from 2 major centers (Royal Melbourne Hospital and The University of Texas MD Anderson Cancer Center), patients with known BRAF mutation status were analyzed for clinical characteristics, survival, and metastatic sites.
  
  
  RESULTS
  The authors identified 524 metastatic CRC patients where BRAF mutation status was known; 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right-sided primary tumor, MSI, and poorer survival (median, 10.4 months vs 34.7 months, P < .001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049). In additional survival analyses, MSI tumors had significantly poorer survival compared with microsatellite stable tumors (22.1 months vs 11.1 months, P = .017), but this difference was not evident in the BRAF mutant population.
  
  
  CONCLUSIONS
  The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. The authors demonstrated that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation.
authors: Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia. Ben.Tran@uhn.on.ca
authors: Ben
authors: B
authors: Tran
authors: Scott
authors: S
authors: Kopetz
authors: Jeanne
authors: J
authors: Tie
authors: Peter
authors: P
authors: Gibbs
authors: Zhi-Qin
authors: ZQ
authors: Jiang
authors: Christopher H
authors: CH
authors: Lieu
authors: Atin
authors: A
authors: Agarwal
authors: Dipen M
authors: DM
authors: Maru
authors: Oliver
authors: O
authors: Sieber
authors: Jayesh
authors: J
authors: Desai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf