title: BRAF Testing in Multifocal Papillary Thyroid Carcinoma.
abstract: BACKGROUND
  BRAF V600E mutation is associated with poor prognosis in patients with papillary thyroid carcinoma (PTC). PTC is often multifocal, and there are no guidelines on how many tumors to test for BRAF mutation in multifocal PTC.
  
  
  METHODS
  Fifty-seven separate formalin-fixed and paraffin-embedded PTCs from twenty-seven patients were manually macrodissected and tested for BRAF mutation using a commercial allele-specific real-time polymerase chain reaction-based assay (Entrogen, Woodland Hills, CA). Data related to histologic characteristics, patient demographics, and clinical outcomes were collected.
  
  
  RESULTS
  All mutations detected were BRAF V600E. Seventeen patients (63%) had concordant mutation status in the largest and second-largest tumors (i.e., both were positive or both were negative). The remaining ten patients (37%) had discordant mutation status. Six of the patients with discordant tumors (22% overall) had a BRAF-negative largest tumor and a BRAF-positive second-largest tumor. No histologic feature was found to help predict which cases would be discordant.
  
  
  CONCLUSIONS
  Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive. Therefore, molecular testing of more than just the dominant tumor should be considered. Future studies are warranted to establish whether finding a BRAF mutation in a smaller tumor has clinical significance.
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue SL-79, New Orleans, LA 70112, USA.
authors.forename: Hillary Z
authors.initials: HZ
authors.lastname: Kimbrell
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue SL-79, New Orleans, LA 70112, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Sholl
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue SL-79, New Orleans, LA 70112, USA.
authors.forename: Swarnamala
authors.initials: S
authors.lastname: Ratnayaka
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue SL-79, New Orleans, LA 70112, USA.
authors.forename: Shanker
authors.initials: S
authors.lastname: Japa
authors.affiliation: Department of Mathematics, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lacey
authors.affiliation: Department of Medicine, Tulane University, 1430 Tulane Avenue SL-12, New Orleans, LA 70112, USA.
authors.forename: Gandahari
authors.initials: G
authors.lastname: Carpio
authors.affiliation: Department of Surgery, Tulane University, 1430 Tulane Avenue SL-22, New Orleans, LA 70112, USA.
authors.forename: Parisha
authors.initials: P
authors.lastname: Bhatia
authors.affiliation: Department of Surgery, Tulane University, 1430 Tulane Avenue SL-22, New Orleans, LA 70112, USA.
authors.forename: Emad
authors.initials: E
authors.lastname: Kandil
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics*; D002291:Carcinoma, Papillary; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008145:Louisiana / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf