title: Specific immunohistochemical detection of the BRAF V600E mutation in primary and metastatic papillary thyroid carcinoma.
abstract: OBJECTIVE
  To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone VE1) for specific detection of the BRAF V600E mutant protein in formalin-fixed paraffin-embedded papillary thyroid carcinoma (PTC) specimens.
  
  
  METHODS
  A total of 118 PTC cases and 116 control cases processed between January 2008 and June 2010 were selected and created tissue microarrays (TMAs) for the study. BRAF V600E (VE1) IHC was performed on tissue sections from PTC cases to determine mutation status. Molecular tests (Sanger sequencing/ARMS) were used to confirm the BRAF V600E gene mutation in primary PTC.
  
  
  RESULTS
  A uniformly cytoplasmic staining throughout the tumors was observed in IHC-positive cases. BRAF V600E was detected in 68.6% (81/118) of PTC samples by IHC and in 61.9% (73/118) by Sanger sequencing/ARMS. The overall concordance between IHC and Sanger sequencing/ARMS was 93.2% (110/118). The sensitivity and specificity of the BRAF V600E IHC was 100% (73/73) and 82.2% (37/45), respectively. Positive and negative predictive values were 90.1% (73/81) and 100% (37/37), respectively. Expression of the BRAF V600E mutant protein was detected in all of 59 cases of primary carcinoma and corresponding metastatic carcinoma in lymph nodes. The concordance between IHC staining in primary and metastatic PTC was 100% (59/59).
  
  
  CONCLUSIONS
  IHC using VE1 antibody for detection of the BRAF V600E mutant protein expression in PTC showed high sensitivity and acceptable specificity, which are critical for diagnostic purposes. IHC staining for BRAF V600E showed uniformly cytoplasmic expression in both primary tumor and metastatic nodes. Therefore, IHC has high practical value for the detection of the BRAF V600E mutation in metastatic and primary PTC.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Shanghai Jiaotong University, Affiliated No. 6th People's Hospital, Shanghai 200233, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: 13524324387@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D002291:Carcinoma, Papillary; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Metastatic; Mutation; Primary; Thyroid carcinoma