Download PDF
Horm Metab Res 2016; 48(03): 157-162
DOI: 10.1055/s-0035-1548873
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Preoperative Assessment of TERT Promoter Mutation on Thyroid Core Needle Biopsies Supports Diagnosis of Malignancy and Addresses Surgical Strategy

A. Crescenzi
1   Pathology Unit, Campus Bio-Medico University Hospital, Rome, Italy
,
P. Trimboli
2   Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy
,
D. C. Modica
3   Section of Pathology, Ospedale Israelitico, Rome, Italy
,
C. Taffon
1   Pathology Unit, Campus Bio-Medico University Hospital, Rome, Italy
,
L. Guidobaldi
3   Section of Pathology, Ospedale Israelitico, Rome, Italy
,
S. Taccogna
4   Section of Pathology, Ospedale Regina Apostolorum, Albano Laziale, Rome, Italy
,
A. Rainer
5   Tissue Engineering Unit, Campus Bio-Medico University, Rome, Italy
,
M. Trombetta
5   Tissue Engineering Unit, Campus Bio-Medico University, Rome, Italy
,
E. Papini
6   Section of Endocrinology, Ospedale Regina Apostolorum, Albano Laziale, Rome, Italy
,
G. Zelano
7   Institute of Human Anatomy and Cell Biology, Sacro Cuore Catholic University Hospital, Rome, Italy
› Author Affiliations
Further Information

Publication History

received 07 January 2015

accepted 12 March 2015

Publication Date:
07 May 2015 (online)

Also available at
   Permissions and Reprints

Abstract

In the last decade, several molecular markers have been proposed to improve the diagnosis of thyroid nodules. Among these, mutations in the telomerase reverse transcriptase (TERT) promoter have been correlated to malignant tumors, characterized by highest recurrence and decreased patients’ survival. This suggests an important role of TERT mutational analysis in the clinical diagnosis and management of thyroid cancer patients. The aim of the study was to demonstrate the adequacy of core needle biopsy (CNB) for the preoperative assessment of TERT mutational status, to reach a more accurate definition of malignancy and a more appropriate surgical planning. Indeed, CNB is gaining momentum for improving diagnosis of thyroid nodules deemed inconclusive by fine needle aspirate (FNA). The study included 50 patients submitted to CNB due to inconclusive FNA report. TERT mutational status was correlated with BRAF mutation, definitive histology, and post-operative TNM staging of the neoplasia. C228T mutation of the TERT promoter was reported in 10% of the papillary carcinomas (PTC) series. When compared with final histology, all cases harboring TERT mutation resulted as locally invasive PTCs. The prevalence of TERT mutated cases was 17.6% among locally advanced PTCs. TERT analysis on CNB allows the assessment of the pathological population on paraffin sections before DNA isolation, minimizing the risk of false negatives due to poor sampling that affects FNA, and gathering aggregate information about morphology and TERT mutational status. Data indicating a worse outcome of the tumor might be used to individualize treatment decision, surgical option, and follow-up design.

Key words

thyroid - cancer - TERT - core needle biopsy (CNB)
 

  • References

  • 1 Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, Coelho R, Celestino R, Prazeres H, Lima L, Melo M, da Rocha AG, Preto A, Castro P, Castro L, Pardal F, Lopes JM, Santos LL, Reis RM, Cameselle-Teijeiro J, Sobrinho-Simões M, Lima J, Máximo V, Soares P. Frequency of TERT promoter mutations in human cancers. Nat Commun 2013; 4: 2185
    PubMedGoogle Scholar
  • 2 Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science 2013; 339: 959-961
    CrossrefPubMedGoogle Scholar
  • 3 Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science 2013; 339: 957-959
    CrossrefPubMedGoogle Scholar
  • 4 Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA, Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He TC, He Y, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Rasheed BA, Riggins GJ, Rosenquist TA, Schiffman M, Shih IM, Theodorescu D, Torbenson MS, Velculescu VE, Wang TL, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013; 110: 6021-6026
    CrossrefPubMedGoogle Scholar
  • 5 Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, Pai S, Bishop J. BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence. J Clin Oncol 2014; 32: 2718-2726
    CrossrefPubMedGoogle Scholar
  • 6 Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, Murugan AK, Guan H, Yu H, Wang Y, Sun H, Shan Z, Teng W, Xing M. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab 2014; 99: E1130-E1136
    CrossrefPubMedGoogle Scholar
  • 7 Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer 2013; 20: 603-610
    CrossrefPubMedGoogle Scholar
  • 8 Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, Celestino R, Almeida A, Salgado C, Eloy C, Castro P, Prazeres H, Lima J, Amaro T, Lobo C, Martins MJ, Moura M, Cavaco B, Leite V, Cameselle-Teijeiro JM, Carrilho F, Carvalheiro M, Máximo V, Sobrinho-Simões M, Soares P. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 2014; 99: E754-E765
    CrossrefPubMedGoogle Scholar
  • 9 Wang N, Liu T, Sofiadis A, Juhlin CC, Zedenius J, Höög A, Larsson C, Xu D. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA. Cancer 2014; 120: 2965-2979
    CrossrefPubMedGoogle Scholar
  • 10 Park KT, Ahn SH, Mo JH, Park YJ, Park dJ, Choi SI, Park SY. Role of core needle biopsy and ultrasonographic finding in management of indeterminate thyroid nodules. Head Neck 2011; 33: 160-165
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 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
    CrossrefPubMedGoogle Scholar
  • 13 Renshaw AA, Pinnar N. Comparison of thyroid fine-needle aspiration and core needle biopsy. Am J Clin Pathol 2007; 128: 370-374
    CrossrefPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Crescenzi A, Guidobaldi L, Nasrollah N, Taccogna S, Cicciarella Modica DD, Turrini L, Nigri G, Romanelli F, Valabrega S, Giovanella L, Onetti Muda A, Trimboli P. Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers. Horm Metab Res 2014; 46: 370-374
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory Notes. New York: Springer Science+Business Media; 2010
    Google Scholar
  • 19 Kocjan G, Cochand-Priollet B, de Agustin PP, Bourgain C, Chandra A, Daneshbod Y, Deery A, Duskova J, Ersoz C, Fadda G, Fassina A, Firat P, Jimenez-Ayala B, Karakitsos P, Koperek O, Matesa N, Poller D, Thienpont L, Ryska A, Schenck U, Sauer T, Schmitt F, Tani E, Toivonen T, Tötsch M, Troncone G, Vass L, Vielh P. Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009. Cytopathology 2010; 21: 86-92
    CrossrefPubMedGoogle Scholar
  • 20 Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, Palombini L, Papini E, Zini M, Pontecorvi A, Vitti P. Italian consensus for the classification and reporting of thyroid cytology. J Endocrinol Invest 2014; 37: 593-599
    CrossrefPubMedGoogle Scholar
  • 21 Trimboli P, Nasrollah N, Guidobaldi L, Taccogna S, Cicciarella Modica DD, Amendola S, Romanelli F, Lenzi A, Nigri G, Centanni M, Giovanella L, Valabrega S, Crescenzi A. The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration. World J Surg Oncol 2014; 12: 61
    CrossrefPubMedGoogle Scholar
  • 22 Hedinger C, Williams ED, Sobin LH. Histological typing of thyroid tumoursWorld Health Organization International histological classification of tumours. Berlin: Springer-Verlag; 2014
    Google Scholar
  • 23 AJCC Cancer Staging Manual. 7th Edition Berlin: Springer; 2010
    Google Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 Cibas ES, Ali SZ. Conference NTFSotS . The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132: 658-665
    CrossrefPubMedGoogle Scholar
  • 26 Wu HH, Jones JN, Osman J. Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital. Diagn Cytopathol 2006; 34: 93-96
    CrossrefPubMedGoogle Scholar
  • 27 Gharib H, Goellner JR. Fine-needle aspiration biopsy of thyroid nodules. Endocr Pract 1995; 1: 410-417
    CrossrefPubMedGoogle Scholar
  • 28 Rago T, Fiore E, Scutari M, Santini F, Di Coscio G, Romani R, Piaggi P, Ugolini C, Basolo F, Miccoli P, Pinchera A, Vitti P. Male sex, single nodularity, and young age are associated with the risk of finding a papillary thyroid cancer on fine-needle aspiration cytology in a large series of patients with nodular thyroid disease. Eur J Endocrinol 2010; 162: 763-770
    CrossrefPubMedGoogle Scholar
  • 29 Gul K, Ersoy R, Dirikoc A, Korukluoglu B, Ersoy PE, Aydin R, Ugras SN, Belenli OK, Cakir B. Ultrasonographic evaluation of thyroid nodules: comparison of ultrasonographic, cytological, and histopathological findings. Endocrine 2009; 36: 464-472
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid 2009; 19: 1351-1361
    CrossrefPubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 Landa I, Ganly I, Chan TA, Mitsutake N, Matsuse M, Ibrahimpasic T, Ghossein RA, Fagin JA. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab 2013; 98: E1562-E1566
    CrossrefPubMedGoogle Scholar
  • 34 Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, Larsson C, Xu D. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 2014; 33: 4978-4984
    CrossrefPubMedGoogle Scholar
  • 35 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. Thyroid 2009; 19: 1167-1214
  • 36 Liu R, Xing M. Diagnostic and prognostic TERT promoter mutations in thyroid fine needle biopsy. Endocr Relat Cancer 2014; 21: 825-830
    CrossrefPubMedGoogle Scholar
  • 37 Harvey JN, Parker D, De P, Shrimali RK, Otter M. Sonographically guided core biopsy in the assessment of thyroid nodules. J Clin Ultrasound 2005; 33: 57-62
    CrossrefPubMedGoogle Scholar
  • 38 Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab 2011; 96: 3390-3397
    CrossrefPubMedGoogle Scholar
  • 39 Stokowy T, Wojtaś B, Fujarewicz K, Jarząb B, Eszlinger M, Paschke R. miRNAs with the potential to distinguish follicular thyroid carcinomas from benign follicular thyroid tumors: results of a meta-analysis. Horm Metab Res 2014; 46: 171-180
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Trimboli P, Treglia G, Giovanella L. Preoperative Measurement of Serum Thyroglobulin to Predict Malignancy in Thyroid Nodules: A Systematic Review. Horm Metab Res 2015; 47: 247-252
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Rosario PW, Penna GC, Calsolari MR. Predictive factors of malignancy in thyroid nodules with repeatedly nondiagnostic cytology (Bethesda category I): value of ultrasonography. Horm Metab Res 2014; 46: 294-298
    Article in Thieme ConnectPubMedGoogle Scholar