title: Co-existence of BRAF V600E Gene Mutation in Tumor and Non-tumoral Surrounding Tissues in Colorectal Cancer.
abstract: OBJECTIVE
  The murine sarcoma viral (V-Raf) oncogene homolog B (BRAF) V600E mutation, which increases protein kinase activity in BRAF-mitogen-activated protein kinase kinase (MEK) - extracellular signal-regulated kinases (ERK) (mitogen-activated protein kinase (MAPK)) signaling, is found in 5-40% of all colorectal carcinoma cases. Proteins with this mutation are reported to be 130-fold more active, which results in induced proliferation, differentiation, cellular survival, and angiogenesis. The aim of the present study was to investigate tumor tissues, together with the surrounding non-tumoral tissues, for BRAF mutation presence, which may be an indicator for possible recurrence or prognosis as in the 'field carcinogenesis' model.
  
  
  METHODS
  The BRAF V600E genotype of 152 colorectal adenocarcinoma paraffin-embedded specimens were determined by mutant-allele-specific amplification-polymerase chain reaction.
  
  
  RESULTS
  According to our results, the presence of BRAF mutation increases risk of lymph node invasion by 1.55-fold [χ(2)=3.83, p=0.05, odds ratio (OR)=1.55, 95% confidence interval (CI)=1.00-2.42], histologically medium or high-grade tumor by 1.60-fold (χ(2)=4.34, p=0.030, OR=1.60, 95% CI=1.03-2.48), vascular invasion by 1.55-fold (χ(2)=3.55, p=0.05, OR=1.55, 95% CI=0.99-2.42), perineural invasion by 1.50-fold (χ(2)=3.16, p=0.07, OR=1.5, 95% CI=0.96-2.33) and the combination of these poor prognostic features by 1.54-fold (χ(2)=2.47, p=0.11, OR=1.54, 95% CI=0.93-2.53). We also found that females are more prone to having the mutation and that being female increases the risk of having this mutation by 1.54-fold (χ(2)=3.58, p=0.05, OR=1.54, 95% CI=0.97-2.44).
  
  
  CONCLUSIONS
  BRAF V600E mutation in non-tumoral surrounding tissue in patients with colorectal cancer may be used as a valuable marker to foresee clinical outcome or a possible recurrence. To our knowledge, this was the first study to take into consideration the non-tumoral surrounding tissues in addition to the tumor tissue.
authors.affiliation: Department of Pathology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey.
authors.forename: Tülin
authors.initials: T
authors.lastname: Öztürk
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Bahar
authors.initials: B
authors.lastname: Toptaş-Hekimoğlu
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Allison Pinar
authors.initials: AP
authors.lastname: Eronat
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Saygili
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Aynur
authors.initials: A
authors.lastname: Dağlar-Aday
authors.affiliation: Faculty of Medicine, Pathology Department, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Nuray
authors.initials: N
authors.lastname: Başsüllü
authors.affiliation: Faculty of Medicine, Pathology Department, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Ilknur
authors.initials: I
authors.lastname: Türkmen
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Hülya Yilmaz
authors.initials: HY
authors.lastname: Aydoğan
authors.affiliation: Faculty of Medicine, Pathology Department, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Gülen
authors.initials: G
authors.lastname: Bülbül
authors.affiliation: Department of Pathology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey Department of Pathology, Acιbadem Maslak Hospital, Istanbul, Turkey.
authors.forename: Süha
authors.initials: S
authors.lastname: Göksel
authors.affiliation: Department of Molecular Medicine, Experimental Medicine and Research Institute, Istanbul University, Istanbul, Turkey.
authors.forename: Oğuz
authors.initials: O
authors.lastname: Öztürk
authors.affiliation: Department of Medical Biology, Yeditepe University, Istanbul, Turkey tisbir@superonline.com.
authors.forename: Turgay
authors.initials: T
authors.lastname: Isbir
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF gene; V600E; colon cancer; field carcinogenesis; mutation