title: Comparing BRAF mutation status in matched primary and metastatic cutaneous melanomas: implications on optimized targeted therapy.
abstract: BACKGROUND
  Selective BRAF inhibitors have shown dramatic results with regard to improving outcome in patients with melanoma. Testing the BRAF status in matched primary and metastatic melanomas to optimize individual targeted therapy is not well investigated.
  
  
  METHODS
  Extended BRAF testing using PCR for 9 mutations and VE1 immunohistochemistry for BRAF V600E detection on 95 lesions including 40 primary melanomas with their matched metastases (n = 42), recurrences (n = 9) and second primaries (n = 4) was performed. Nine patients had multiple metastases.
  
  
  RESULTS
  V600E was the only identified mutation type; 35.4% of primary vs. 18.9% of metastatic melanomas. The overall primary-metastatic BRAF status discordance rate was 32.3% using PCR and 27.5% with immunohistochemistry, and was significantly more frequent in primary lesions with mutant BRAF (67%). Males and patients with metastasis to lymph nodes were less likely to be discordant compared to females and those with metastasis to other sites (p = 0.023). Discordant BRAF mutation status was predicted by multivariate binary logistic regression: the presence of a mutant BRAF in the primary melanoma [OR (95% C.I.) = 23.4 (2.4-229.7)] and female gender [OR = 10.6 (1.08-95)]. Inter-metastases BRAF concordance was 100% (6 comparisons).
  
  
  CONCLUSIONS
  A high discordant rate implies the need for clinical trials addressing the response to targeted therapy in patients with discordant BRAF statuses between their primary and metastatic lesions.
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Maya
authors.initials: M
authors.lastname: Saroufim
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Habib
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Rita
authors.initials: R
authors.lastname: Gerges
authors.affiliation: Weill-Cornell Medical Center, New York, NY, United States.
authors.forename: Jad
authors.initials: J
authors.lastname: Saab
authors.affiliation: Shaukat Khanum Memorial Cancer Centre and Research Hospital, Lahore, Pakistan.
authors.forename: Asif
authors.initials: A
authors.lastname: Loya
authors.affiliation: King Fahad Specialist Hospital, Dammam, Saudi Arabia.
authors.forename: Samir S
authors.initials: SS
authors.lastname: Amr
authors.affiliation: Dhahran Health Center, SAMSO, Dhahran, Saudi Arabia.
authors.forename: Salwa
authors.initials: S
authors.lastname: Sheikh
authors.affiliation: King Abdul-Aziz Medical City, Jeddah, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Satti
authors.affiliation: Weill-Cornell Medical Center, New York, NY, United States; ViennaLab Diagnostics GmbH, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.affiliation: American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: ik08@aub.edu.lb.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khalifeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Matched primary and metastatic melanomas; Targeted therapy