title: Allele percentage of the BRAF V600E mutation in papillary thyroid carcinomas and corresponding lymph node metastases: no evidence for a role in tumor progression.
abstract: BACKGROUND
  The relevance of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) as a negative prognostic factor is a subject of intense debate. This mutation has been associated with several clinicopathological features, but the lack of consistency among data does not support its usefulness as marker of tumor aggressiveness and poorer outcome. Due to the genetic heterogeneity of the tumor, both the occurrence and the allele percentage of the BRAF mutation should be considered to unravel this controversy.
  
  
  OBJECTIVE
  We aimed to evaluate the impact of the BRAF V600E mutation occurrence and the allele percentage on the metastatic process in PTCs.
  
  
  METHODS
  The presence and allele percentage of the BRAF mutation were determined by pyrosequencing in 132 cases of well-differentiated PTCs with (n = 37) or without lymph node metastases (LNMs) (n = 95) and in 40 LNMs matched with 35 PTCs.
  
  
  RESULTS
  No significant differences were observed in either the occurrence or the allele percentage of V600E mutation between the 2 groups of PTCs with or without LNMs. The LNMs were heterogeneous for the V600E mutation as the primary lesions.
  
  
  CONCLUSIONS
  In this study, the occurrence and percentage of the BRAF V600E mutated allele was not preferentially associated with the development of metastases and the average mutated allele percentage decreased as the tumor progresses from the primary site to the lymph node metastatic sites. These observations support the need to reevaluate the role of the BRAF V600E mutation as a negative prognostic marker in PTCs.
authors.affiliation: Laboratory of Molecular Biology, Department of Oncology, Arcispedale S. Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.forename: Valentina
authors.initials: V
authors.lastname: Sancisi
authors.forename: Federica
authors.initials: F
authors.lastname: Torricelli
authors.forename: Moira
authors.initials: M
authors.lastname: Ragazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Frasoldati
authors.forename: Simonetta
authors.initials: S
authors.lastname: Piana
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000556:secondary*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf