title: The Frequency and Clinical Implications of the BRAF(V600E) Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades.
abstract: BACKGROUND
  Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF(V600E), which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF(V600E) mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.
  
  
  METHODS
  The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAF(V600E) mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.
  
  
  RESULTS
  The prevalence of the BRAF(V600E) mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAF(V600E) mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAF(V600E) mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAF(V600E) mutation status.
  
  
  CONCLUSIONS
  The BRAF(V600E) mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAF(V600E)-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAF(V600E) mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: A Ram
authors.initials: AR
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.; Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyuk
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.; Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Hoon Sung
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.; Department of Internal Medicine, Dankook University Hospital, Cheonan, Korea.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Yoo
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Won
authors.affiliation: Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yjparkmd@snu.ac.kr.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
keywords: BRAF(V600E) mutation; Prognosis; Thyroid cancer, papillary