title: The role of K-RAS and B-RAF mutations as biomarkers in metastatic colorectal cancer.
abstract: OBJECTIVE
  Unlike cetuximab, there is a paucity of biomarkers for bevacizumab as predictors of outcome in metastatic colorectal cancer (mCRC) patients. Obviously exploring the worth of some potential markers in this setting is warranted. The purpose of this study was to investigate the predictive value of the presence of K-RAS and B-RAF mutations on the outcome of patients with mCRC treated with FOLFIRI and bevacizumab combination therapy.
  
  
  METHODS
  A total of 172 patients with mCRC were evaluated. K-RAS and B-RAF mutations were analyzed by quantitative PCR. Median progression-free survival (PFS) and overall survival (OS) were compared utilizing chi-square and Mann-Whitney U tests, respectively.
  
  
  RESULTS
  Forty-four percent (N=77) of the patients were found to harbor K-RAS mutations and 6 (7.5%) were positive for B-RAF mutations. In baseline no difference in PFS and OS was observed between the groups with or without K-RAS mutation. No relationship was established between K-RAS and B-RAF mutation status and baseline CEA and CA19-9 tumor markers levels.
  
  
  CONCLUSIONS
  K-RAS and B-RAF mutations do not seem to be predictive of treatment outcome as potential biomarkers for bevacizumab therapy in mCRC. However, not only the presence of K-RAS and B-RAF mutations but also the different biological behavior of the various subtypes of mutations should be considered as potential determinants in the final outcome of this disease.
authors.affiliation: University of Istanbul, Cerrahpasa Medical Faculty, Istanbul, Turkey. drfatih74@yahoo.com
authors.forename: F
authors.initials: F
authors.lastname: Selcukbiricik
authors.forename: S
authors.initials: S
authors.lastname: Erdamar
authors.forename: C U
authors.initials: CU
authors.lastname: Ozkurt
authors.forename: N
authors.initials: N
authors.lastname: Molinas Mandel
authors.forename: F
authors.initials: F
authors.lastname: Demirelli
authors.forename: M
authors.initials: M
authors.lastname: Ozguroglu
authors.forename: D
authors.initials: D
authors.lastname: Tural
authors.forename: E
authors.initials: E
authors.lastname: Buyukunal
authors.forename: S
authors.initials: S
authors.lastname: Serdengecti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000068258:Bevacizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin