title: Detection of plasma BRAF(V600E) mutation is associated with lung metastasis in papillary thyroid carcinomas.
abstract: OBJECTIVE
  The BRAF(V600E) mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF(V600E) in predicting the advanced disease of PTC.
  
  
  METHODS
  Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF(V600E) mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  The BRAF(V600E) mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF(V600E) mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF(V600E) mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis.
  
  
  CONCLUSIONS
  These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF(V600E) mutation in large prospective studies.
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.; Biomedical Research Institute, Busan, Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.; Biomedical Research Institute, Busan, Korea. injkim@pusan.ac.kr.
authors.forename: In Joo
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Jin Choon
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: In Suk
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Seong-Jang
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Kim Yong Ki Internal Medicine Clinic, Busan, Korea.
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020135:Peptide Nucleic Acids; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D020135:Peptide Nucleic Acids; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; DNA; biomarker; papillary thyroid carcinoma; plasma
references.citation: J Clin Endocrinol Metab. 2007 Nov;92(11):4085-90
references.pmid: 17785355
references.citation: Ann Surg. 2007 Sep;246(3):466-70; discussion 470-1
references.pmid: 17717450
references.citation: Clin Endocrinol (Oxf). 2008 Oct;69(4):683-5
references.pmid: 18363883
references.citation: J Clin Endocrinol Metab. 2008 Oct;93(10):3943-9
references.pmid: 18682506
references.citation: Surgery. 2008 Dec;144(6):1070-7; discussion 1077-8
references.pmid: 19041020
references.citation: J Clin Endocrinol Metab. 2009 May;94(5):1612-7
references.pmid: 19190105
references.citation: J Clin Endocrinol Metab. 2009 Dec;94(12):5001-9
references.pmid: 19850689
references.citation: Head Neck. 2010 Feb;32(2):229-34
references.pmid: 19626635
references.citation: Pathol Res Pract. 2011 Dec 15;207(12):762-8
references.pmid: 22070922
references.citation: Ann Surg Oncol. 2013 Mar;20(3):759-66
references.pmid: 23179992
references.citation: Am J Clin Pathol. 2013 Jun;139(6):759-64
references.pmid: 23690118
references.citation: Endocr Pract. 2000 Nov-Dec;6(6):469-76
references.pmid: 11155222
references.citation: ORL J Otorhinolaryngol Relat Spec. 2001 Jul-Aug;63(4):243-9
references.pmid: 11408821
references.citation: World J Surg. 2002 Jan;26(1):22-8
references.pmid: 11898029
references.citation: Yonsei Med J. 2004 Oct 31;45(5):818-21
references.pmid: 15515191
references.citation: N Engl J Med. 1993 Feb 25;328(8):553-9
references.pmid: 8426623
references.citation: Surg Oncol Clin N Am. 1996 Jan;5(1):43-63
references.pmid: 8789493
references.citation: Yonsei Med J. 1998 Aug;39(4):355-62
references.pmid: 9752802
references.citation: Virchows Arch. 2005 Jun;446(6):589-95
references.pmid: 15902486
references.citation: Clin Endocrinol (Oxf). 2005 Nov;63(5):588-93
references.pmid: 16268813
references.citation: Endocr Relat Cancer. 2006 Mar;13(1):257-69
references.pmid: 16601293
references.citation: Arch Surg. 2006 May;141(5):489-94; discussion 494-6
references.pmid: 16702521
references.citation: World J Surg. 2006 Jun;30(6):1088-95
references.pmid: 16736341
references.citation: Clin Endocrinol (Oxf). 2006 Sep;65(3):364-8
references.pmid: 16918957
references.citation: J Clin Endocrinol Metab. 2007 Jun;92(6):2264-71
references.pmid: 17374713
references.citation: Cancer. 2007 Jul 1;110(1):38-46
references.pmid: 17520704
references.citation: Endocr Rev. 2007 Dec;28(7):742-62
references.pmid: 17940185