title: BRAF V600E mutation is associated with tumor aggressiveness in papillary thyroid cancer.
abstract: BACKGROUND
  The BRAF(V600E) mutation is the most common genetic alteration found in papillary thyroid cancer (PTC). Recent studies show that this mutation occurs more frequently in patients with PTC showing aggressive clinicopathologic features. The aim of the present study was to evaluate the prevalence of the BRAF(V600E) mutation in tumor samples and its association with high-risk clinicopathologic features prospectively.
  
  
  METHODS
  From February 2009 to January 2010, 547 PTC patients who underwent surgery in Seoul National University Hospital were enrolled in the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF(V600E) mutation. Both univariate and multivariate analyses were performed to analyze associations between the BRAF(V600E) mutation and clinicopathologic features.
  
  
  RESULTS
  The BRAF(V600E) mutation was found in 381/547 (69.7%) patients with primary PTC. The BRAF(V600E) mutation was significantly associated with age (≥ 45 years), tumor size (>1 cm), extrathyroidal extension, and cervical lymph node metastases (P < 0.05). Multiple logistic regression showed that it was significantly associated with gender (OR = 1.834; 95% CI 1.021-3.463), tumor size (OR = 1.972; 95% CI 1.250-3.103), and extra-thyroidal extension (OR = 2.428; 95% CI 1.484-3.992), but not with age, multifocality, lymph node metastases, and advanced disease stage. The proportion of BRAF(V600E) mutation was significantly associated with the number of high-risk factors of tumor recurrence (P < 0.001).
  
  
  CONCLUSIONS
  The BRAF(V600E) mutation was associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF(V600E) mutation may be a potential prognostic factor in PTC patients.
authors.affiliation: Department of Surgery, Haeundae Paik Hospital, Inje University College of Medicine, 1435 Jwa-dong, Haeundae-gu, Busan, 612-030, Korea. su.jin.kim.md@gmail.com
authors.forename: Su-jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Jun Pyo
authors.initials: JP
authors.lastname: Myong
authors.forename: Jeong-hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Do Hoon
authors.initials: do H
authors.lastname: Koo
authors.forename: Yeo-Kyu
authors.initials: YK
authors.lastname: Youn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D056910:Republic of Korea; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf