title: BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC) in daily clinical practice: correlations with clinical characteristics, and its impact on patients' outcome.
abstract: BACKGROUND
  To prospectively evaluate the usefulness of the BRAFV600E mutation detection in daily clinical practice in patients with metastatic Colorectal Cancer (mCRC).
  
  
  METHODS
  504 mCRC patients treated with systemic chemotherapy ± biologics were analyzed.
  
  
  RESULTS
  A statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p=0.001), multiple metastatic sites (p=0.002),> 65 years old (p=0.004), primary tumors located in the colon (p<0.001), high-grade tumors (p=0.001) and in those with mucinous features (p=0.037). Patients with BRAFV600E mutated tumors had a statistically significantly reduced progression-free survival (PFS) compared to wild-type (wt) ones (4.1 and 11.6 months, respectively; p<0.001) and overall survival (OS) (14.0 vs. 34.6 months, respectively; p<0.001). In the multivariate analysis the BRAFV600E mutation emerged as an independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7-6.2; p<0.001) and OS (HR: 5.9, 95% CI 3.7-9.5; p<0.001). Among the 273 patients treated with salvage cetuximab or panitumumab, the BRAFV600E mutation was correlated with reduced PFS (2.2 vs. 6.0 months; p<0.0001) and OS (4.3 vs. 17.4 months; p<0.0001).
  
  
  CONCLUSIONS
  The presence of BRAFV600E-mutation in mCRC characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients' prognosis.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece ; Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: Zacharenia
authors.initials: Z
authors.lastname: Saridaki
authors.affiliation: Laboratory of Pathology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tzardi
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sfakianaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Chara
authors.initials: C
authors.lastname: Papadaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Voutsina
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Aristea
authors.initials: A
authors.lastname: Kalykaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Ippokratis
authors.initials: I
authors.lastname: Messaritakis
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Mpananis
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece ; Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.affiliation: Laboratory of Pathology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Stathopoulos
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece ; Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece ; Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
mesh_terms: D000367:Age Factors; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins