title: Clinicopathologic implications of the BRAF(V600E) mutation in papillary thyroid cancer: a subgroup analysis of 3130 cases in a single center.
abstract: BACKGROUND
  The BRAF mutation has been shown to be associated with aggressive clinicopathologic characteristics of papillary thyroid cancer (PTC). However, several studies that analyzed hundreds of patients have not demonstrated any correlation. The objective of this study was to investigate the relationship of the BRAF mutation with clinicopathologic factors in a large group of homogenous PTC patients.
  
  
  METHODS
  We collected data of PTC patients who received curative resection of the thyroid gland and who had undergone BRAF mutation tests of their thyroid cancer tissue. Minor variant PTCs and mixed-type thyroid cancers were excluded in this analysis. Clinicopathologic characteristics, including age, sex, BRAF mutation, tumor histology, size, extrathyroidal extension, tumor margin, lymph node metastasis, multifocality, stage, and associated thyroid disease, were collected. The relationship of the BRAF mutation with clinicopathologic factors was analyzed in each homogenous histologic PTC.
  
  
  RESULTS
  There were 3130 PTC patients who met the criteria, and these patients were divided into three major histologic groups: conventional PTC (n = 2947), diffuse sclerosing variant PTC (n = 98), and follicular variant PTC (n = 85). The BRAF mutation was variably detected in 75.3%, 61%, and 40% of patients, respectively. In conventional PTC cases, the BRAF mutation was significantly associated with large tumor size, extrathyroidal extension, and lymph node metastasis. Coexistent chronic lymphocytic thyroiditis was significantly less prevalent in the BRAF mutant group. Age, sex, and tumor margin status were not significantly correlated with the BRAF status. There was no evidence that any clinicopathologic factors were linked with the BRAF mutation status in diffuse sclerosing and follicular variant PTCs.
  
  
  CONCLUSIONS
  The BRAF mutation was differentially detected in each histologic subtype of PTC and was strongly correlated with pathologic factors, most strongly with no coexistent chronic lymphocytic thyroiditis, in conventional PTC. The BRAF mutation is suggested to be a poor prognostic marker in conventional PTC, and the BRAF mutational analysis may lead to better management for individual PTC patients.
authors.affiliation: 1 Department of Medical Oncology, Thyroid Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine , Seoul, Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Lim
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Bup-Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Cheong Soo
authors.initials: CS
authors.lastname: Park
authors.forename: Hang-Seok
authors.initials: HS
authors.lastname: Chang
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Cho
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000601:surgery; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery; D013966:Thyroiditis / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf