Download PDF
Horm Metab Res 2014; 46(05): 370-374
DOI: 10.1055/s-0034-1368700
Immediate Interest
© Georg Thieme Verlag KG Stuttgart · New York

Immunohistochemistry for BRAF(V600E) Antibody VE1 Performed in Core Needle Biopsy Samples Identifies Mutated Papillary Thyroid Cancers

A. Crescenzi
1   Section of Pathology, Ospedale Israelitico, Rome, Italy
,
L. Guidobaldi
1   Section of Pathology, Ospedale Israelitico, Rome, Italy
,
N. Nasrollah
2   Section of Surgery, Ospedale Israelitico, Rome, Italy
,
S. Taccogna
3   Section of Pathology, Ospedale Regina Apostolorum/IHG2, Albano Laziale (Rome), Italy
,
D. D. Cicciarella Modica
1   Section of Pathology, Ospedale Israelitico, Rome, Italy
,
L. Turrini
3   Section of Pathology, Ospedale Regina Apostolorum/IHG2, Albano Laziale (Rome), Italy
,
G. Nigri
4   Department of Surgical and Medical Sciences, Sapienza University, Ospedale S. Andrea, Rome, Italy
,
F. Romanelli
5   Department of Experimental Medicine, Sapienza University, Rome, Italy
,
S. Valabrega
4   Department of Surgical and Medical Sciences, Sapienza University, Ospedale S. Andrea, Rome, Italy
,
L. Giovanella
6   Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
,
A. Onetti Muda
7   Integrated Research Center (CIR), Campus Bio-Medico University, Rome, Italy
,
P. Trimboli
8   Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy
› Author Affiliations
Further Information

Publication History

received 21 October 2013

accepted 21 January 2014

Publication Date:
25 February 2014 (online)

Also available at
    Permissions and Reprints

Abstract

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines 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 nonthyroid 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 following 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 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry 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 immunohistochemistry 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.

Key words

thyroid - cancer - BRAF(V600E) - VE1 - core needle biopsy (CNB)
 

  • References

  • 1 Kato MA, Fahey 3rd TJ. Molecular markers in thyroid cancer diagnostics. Surg Clin North Am 2009; 89: 1139-1155
    CrossrefPubMedSearch in Google Scholar
  • 2 de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpcao LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005; 47: 391-401
    CrossrefPubMedSearch in Google Scholar
  • 3 Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, Orlandi F, Papotti M. Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer 2005; 12: 305-317
    CrossrefPubMedSearch in Google Scholar
  • 4 Eszlinger M, Paschke R. Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol 2010; 322: 29-37
    CrossrefPubMedSearch in Google Scholar
  • 5 Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid 2009; 19: 1351-1361
    CrossrefPubMedSearch in Google Scholar
  • 6 Couto JP, Prazeres H, Castro P, Lima J, Máximo V, Soares P, Sobrinho-Simões M. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol 2009; 62: 414-421
    CrossrefPubMedSearch in Google Scholar
  • 7 Elisei R, Viola D, Torregrossa L, Giannini R, Romei C, Ugolini C, Molinaro E, Agate L, Biagini A, Lupi C, Valerio L, Materazzi G, Miccoli P, Piaggi P, Pinchera A, Vitti P, Basolo F. The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab 2012; 97: 4390-4398
    CrossrefPubMedSearch in Google Scholar
  • 8 Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O’Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Tufano RP, Pai SI, Zeiger MA, Westra WH, Clark DP, Clifton-Bligh R, Sidransky D, Ladenson PW, Sykorova V. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 2013; 309: 1493-1501
    CrossrefPubMedSearch in Google Scholar
  • 9 Boufraqech M, Patel D, Xiong Y, Kebebew E. Diagnosis of thyroid cancer: state of art. Expert Opin Med Diagn 2013; 7: 331-342
    CrossrefPubMedSearch in Google Scholar
  • 10 Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, Vitti P. AACE/AME/ETA Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules. Endocr Pract 2010; 1: 1-43
    PubMedSearch in Google Scholar
  • 11 American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer . Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214
    Search in Google Scholar
  • 12 Long GV, Wilmott JS, Capper D, Preusser M, Zhang YE, Thompson JF, Kefford RF, von Deimling A, Scolyer RA. Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol 2013; 37: 61-65
    CrossrefPubMedSearch in Google Scholar
  • 13 Ilie M, Long E, Hofman V, Dadone B, Marquette CH, Mouroux J, Vignaud JM, Begueret H, Merlio JP, Capper D, von Deimling A, Emile JF, Hofman P. Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. Ann Oncol 2013; 24: 742-748
    CrossrefPubMedSearch in Google Scholar
  • 14 Capper D, Preusser M, Habel A, Sahm F, Ackermann U, Schindler G, Pusch S, Mechtersheimer G, Zentgraf H, von Deimling A. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol 2011; 122: 11-19
    CrossrefPubMedSearch in Google Scholar
  • 15 Park KT, Ahn SH, Mo JH, Park YJ, Park J, Choi SI, Park SY. Role of core needle biopsy and ultrasonographic finding in management of indeterminate thyroid nodules. Head Neck 2011; 33: 160-165
    CrossrefPubMedSearch in Google Scholar
  • 16 Zhang S, Ivanovic M, Nemcek Jr. AA, Defrias DV, Lucas E, Nayar R. Thin core needle biopsy crush preparations in conjunction with fine-needle aspiration for the evaluation of thyroid nodules: a complementary approach. Cancer (Cancer Cytopathology) 2008; 114: 512-518
    CrossrefPubMedSearch in Google Scholar
  • 17 Screaton NJ, Berman LH, Grant JW. US-guided Core-Needle Biopsy of the Thyroid Gland. Radiology 2003; 226: 827-832
    CrossrefPubMedSearch in Google Scholar
  • 18 Sung JY, Na DG, Kim KS, Yoo H, Lee H, Kim JH, Baek JH. Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort. Eur Radiol 2012; 22: 1564-1572
    CrossrefPubMedSearch in Google Scholar
  • 19 Na DG, Kim JH, Sung JY, Baek JH, Jung KC, Lee H, Yoo H. Core-Needle Biopsy Is More Useful Than Repeat Fine-Needle Aspiration in Thyroid Nodules Read as Nondiagnostic or Atypia of Undetermined Significance by the Bethesda System for Reporting Thyroid Cytopathology. Thyroid 2012; 22: 468-475
    CrossrefPubMedSearch in Google Scholar
  • 20 Samir AE, Vij A, Seale MK, Desai G, Halpern E, Faquin WC, Parangi S, Hahn PF, Daniels GH. Ultrasound-guided percutaneous thyroid nodule core biopsy: clinical utility in patients with prior nondiagnostic fine-needle aspirate. Thyroid 2012; 22: 461-467
    CrossrefPubMedSearch in Google Scholar
  • 21 Nasrollah N, Trimboli P, Guidobaldi L, Cicciarella Modica DD, Ventura C, Ramacciato G, Taccogna S, Romanelli F, Valabrega S, Crescenzi A. Thin core biopsy should help to discriminate thyroid nodules cytologically classified as indeterminate. A new sampling technique. Endocrine 2013; 43: 659-665
    PubMedSearch in Google Scholar
  • 22 Nasrollah N, Trimboli P, Rossi F, Amendola S, Guidobaldi L, Ventura C, Maglio R, Nigri G, Romanelli F, Valabrega S, Crescenzi A. Patient’s comfort with and tolerability of thyroid core needle biopsy. Endocrine 2014; 45: 79-83
    CrossrefPubMedSearch in Google Scholar
  • 23 Renshaw AA, Pinnar N. Comparison of thyroid fine-needle aspiration and core needle biopsy. Am J Clin Pathol 2007; 128: 370-374
    CrossrefPubMedSearch in Google Scholar
  • 24 De Lellis R, Lloyd R, Heitz P, Eng C. Pathology and genetics of tumour of endocrine organs. In: Kleihues P, Sobin L. (eds.). World Health Organization Classification of Tumours. Lyon, France: IARC; 2004: 49-133
    Search in Google Scholar
  • 25 Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer 2005; 12: 245-262
    CrossrefPubMedSearch in Google Scholar
  • 26 Zimmermann AK, Camenisch U, Rechsteiner MP, Bode-Lesniewska B, Rössle M. Value of immunohistochemistry in the detection of BRAF V600E mutations in fine-needle aspiration biopsies of papillary thyroid carcinoma. Cancer Cytopathol 2014; 122: 48-58
    CrossrefPubMedSearch in Google Scholar
  • 27 Vivero M, Kraft S, Barletta JA. Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid 2013; 23: 273-279
    CrossrefPubMedSearch in Google Scholar
  • 28 Cradic KW, Milosevic D, Rosenberg AM, Erickson LA, McIver B, Grebe SK. Mutant BRAF(T1799A) can be detected in the blood of papillary thyroid carcinoma patients and correlates with disease status. J Clin Endocrinol Metab 2009; 94: 5001-5009
    CrossrefPubMedSearch in Google Scholar
  • 29 Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012; 367: 705-715
    CrossrefPubMedSearch in Google Scholar
  • 30 Fadda G, Basolo F, Bondi A, Bussolati G, Crescenzi A, Nappi O, Nardi F, Papotti M, Taddei G, Palombini L. Cytological classification of thyroid nodules. Proposal of the SIAPEC-IAP Italian Consensus Working Group. Pathologica 2010; 102: 405-408
    PubMedSearch in Google Scholar