title: Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma.
abstract: BACKGROUND
  The BRAF(V600E) mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAF(V600E) mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC.
  
  
  METHODS
  This study included 467 patients with PTC who underwent surgical resection. We studied the BRAF(V600E) mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA).
  
  
  RESULTS
  The frequencies of a positive BRAF(V600E) mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAF(V600E) mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAF(V600E) mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAF(V600E) mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant.
  
  
  CONCLUSIONS
  Our results showed that positive BRAF V600E IHC significantly correlated with the BRAF(V600E) mutation. This suggests its clinical utility as a screening tool for the BRAF(V600E) mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAF(V600E) mutation-positive cases of PTC.
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Yoon Yang
authors.initials: YY
authors.lastname: Jung
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Eon Sub
authors.initials: ES
authors.lastname: Park
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Yun Jae
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea; Thyroid Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea. Electronic address: hkim1967@gmail.com.
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012313:RNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E mutation; Immunohistochemistry; Papillary carcinoma; RNA in situ hybridization