370 Immediate Interest Crescenzi A et al. VE1 Expression on Thyroid Microhistology… Horm Metab Res 2014; 46: 370–374 received 21.10.2013 accepted 21.01.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1368700 Published online: February 25, 2014 Horm Metab Res 2014; 46: 370–374 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence Dr. A. Crescenzi Anatomia Patologica Ospedale Israelitico di Roma Via Fulda, 14 00148 Rome Italy Tel.: + 39/06/655 891 Fax: + 39/06/655 89329 crescenzianna@libero.it Key words ● ▶ thyroid ● ▶ cancer ● ▶ BRAF(V600E) ● ▶ VE1 ● ▶ core needle biopsy (CNB) Immunohistochemistry for BRAF(V600E) Antibody VE1 Performed in Core Needle Biopsy Samples Identifies Mutated Papillary Thyroid Cancers related mortality among PTC patients [8]. Unfor- tunately, current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration (FNA) owing to several reasons [9–11]. Currently, the relationship between immunohistochemistry for VE1, a mouse anti-human BRAF(V600E) anti- body, and BRAF genotyping is under investigation, and a strong correlation with BRAF-mutated non- thyroid cancers has been reported [12–14]. The microhistologic evaluation of samples obtained by core needle biopsy (CNB) has been proposed as a complementary test for thyroid nodules with inconclusive FNA. By CNB, a very large percentage of nodules that are read as inad- equate or indeterminate at cytologic examina- tion may be re-assessed as diagnostic, with high tolerability and good comfort for patients [15– 23]. To date, immunohistochemistry using VE1 has not been investigated in thyroid CNB speci- mens. Introduction ▼ In the last decade, the risk stratification of thyroid nodules has been improved by several immuno- histochemical and molecular markers [1]. While galectin-3, HBME-1 and cytokeratin-19 have been recognized as a reliable panel to predict thyroid malignancy [2, 3], molecular analyses, such as of BRAF, RAS, RET/PTC, and PAX8/PPAR have been associated with higher cancer aggressiveness and their use has been proposed for clinical evaluation [4–6]. In particular, great relevance has been ascribed to the V600E mutation of the BRAF gene [BRAF(V600E)]. The latter, which involves substi- tution of glutamate (E) for valine (V) at codon 600, is found in 30–70 % of papillary thyroid carcino- mas (PTC) and has been reported as an independ- ent predictor of poor prognosis, also in patients with intrathyroid PTC clinically at low-risk of recurrence [7]. Furthermore, in a large retrospec- tive multicenter study, BRAF(V600E) mutation seemed to be associated with increased cancer- Authors A. Crescenzi 1 , L. Guidobaldi 1 , N. Nasrollah 2 , S. Taccogna 3 , D. D. Cicciarella Modica 1 , L. Turrini 3 , G. Nigri 4 , F. Romanelli 5 , S. Valabrega 4 , L. Giovanella 6 , A. Onetti Muda 7 , P. Trimboli 8 Abstract ▼ BRAF(V600E) is the most frequent genetic muta- tion in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guide- lines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthy- roid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery fol- lowing CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 ade- nomatous nodules. One follicular thyroid can- cer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immuno- histochemistry revealed 8 mutated PTC and 22 negative cases. A 100 % agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immu- nohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery. Affiliations Affiliation addresses are listed at the end of the article This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.