title: A modified Lynch syndrome screening algorithm in colon cancer: BRAF immunohistochemistry is efficacious and cost beneficial.
abstract: OBJECTIVE
  Somatic BRAF mutation in colon cancer essentially excludes Lynch syndrome. We compared BRAF V600E immunohistochemistry (IHC) with BRAF mutation in core, biopsy, and whole-section slides to determine whether IHC is similar and to assess the cost-benefit of IHC.
  
  
  METHODS
  Resection cases (2009-2013) with absent MLH1 and PMS2 and prior BRAF mutation polymerase chain reaction results were chosen (n = 57). To mimic biopsy specimens, tissue microarrays (TMAs) were constructed. In addition, available biopsies performed prior to the resection were available in 15 cases. BRAF V600E IHC was performed and graded on TMAs, available biopsy specimens, and whole-section slides. Mutation status was compared with IHC, and cost-benefit analysis was performed.
  
  
  RESULTS
  BRAF V600E IHC was similar in TMAs, biopsy specimens, and whole-section slides, with only four (7%) showing discordance between IHC and mutation status. Using BRAF V600E IHC in our Lynch syndrome screening algorithm, we found a 10% cost savings compared with mutational analysis.
  
  
  CONCLUSIONS
  BRAF V600E IHC was concordant between TMAs, biopsy specimens, and whole-section slides, suggesting biopsy specimens are as useful as whole sections. IHC remained cost beneficial compared with mutational analysis, even though more patients needed additional molecular testing to exclude Lynch syndrome.
authors.affiliation: From the Department of Pathology and Rachel.Roth@osumc.edu.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Roth
authors.affiliation: Department of Human Genetics, The Ohio State University Wexner Medical Center, Columbus.
authors.forename: Heather
authors.initials: H
authors.lastname: Hampel
authors.affiliation: From the Department of Pathology and.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Arnold
authors.affiliation: From the Department of Pathology and.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Yearsley
authors.affiliation: From the Department of Pathology and.
authors.forename: William L
authors.initials: WL
authors.lastname: Marsh
authors.affiliation: From the Department of Pathology and.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019943:Amino Acid Substitution; D001706:Biopsy; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000473:pathology*; D003362:Cost-Benefit Analysis; D004252:DNA Mutational Analysis; D004502:Education, Medical, Continuing; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Cost-benefit analysis; Immunohistochemistry; MLH1