Skip to main content

Advertisement

SpringerLink
Log in

Ultrasonographic prediction of highly aggressive telomerase reverse transcriptase (TERT) promoter-mutated papillary thyroid cancer

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Telomerase reverse transcriptase promoter mutations are found in highly aggressive thyroid malignancies. Our aim was to define the ultrasonographic features of telomerase reverse transcriptase promoter-mutated papillary thyroid cancer and to evaluate their predictive performances.

Methods

Ultrasonographic findings were reviewed for 185 patients with surgically confirmed papillary thyroid cancer between 1994 and 2004. Genomic DNA to identify telomerase reverse transcriptase promoter mutations was extracted from archived surgical specimens. Logistic regression analysis was performed to compare clinical factors and ultrasonographic findings between telomerase reverse transcriptase promoter-mutated and wild-type papillary thyroid cancers.

Results

A telomerase reverse transcriptase promoter mutation was detected in 8.1% (15 of 185) of specimens from papillary thyroid cancer patients with a strong trend toward increasing age. Nonparallel orientation and microlobulated margin were independent ultrasonographic findings for predicting telomerase reverse transcriptase promoter-mutated papillary thyroid cancer in patients over 50 years (odds ratio 5.898, 95% confidence interval 1.092–31.851, P = 0.039 for orientation; odds ratio 5.813, 95% confidence interval 1.320–25.602, P = 0.020 for margin). Prevalence of telomerase reverse transcriptase promoter mutations increased to 50.0% in papillary thyroid cancer patients older than 50 years with both ultrasonographic findings and was 0% in patients without either finding. For identifying telomerase reverse transcriptase promoter-mutated papillary thyroid cancer, ultrasonographic had 64.3% sensitivity, 80.8% specificity, 50.0% positive predictive value and 88.4% negative predictive value.

Conclusions

Telomerase reverse transcriptase promoter-mutated papillary thyroid cancer could be suggested by the ultrasonographic features of nonparallel orientation and microlobulated margin in patients older than 50 years. Prebiopsy recognition of this unique ultrasonographic pattern would mandate the nodule fall into a “biopsy suggested” category.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. R. Liu, M. Xing, TERT promoter mutations in thyroid cancer. Endocr. Relat. Cancer 23, R143–R155 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. T.H. Kim, Y.E. Kim, S. Ahn, J.Y. Kim, C.S. Ki, Y.L. Oh, K. Kim, J.W. Yun, W.Y. Park, J.H. Choe, J.H. Kim, J.S. Kim, S.W. Kim, J.H. Chung, TERT promoter mutations and long-term survival in patients with thyroid cancer. Endocr. Relat. Cancer 23, 813–823 (2016)

    Article  PubMed  Google Scholar 

  3. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26, 1–133 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  4. D. de Biase, G. Gandolfi, M. Ragazzi, M. Eszlinger, V. Sancisi, M. Gugnoni, M. Visani, A. Pession, G. Casadei, C. Durante, G. Costante, R. Bruno, M. Torlontano, R. Paschke, S. Filetti, S. Piana, A. Frasoldati, G. Tallini, A. Ciarrocchi, TERT promoter mutations in papillary thyroid microcarcinomas. Thyroid 25, 1013–1019 (2015)

    Article  PubMed  Google Scholar 

  5. Cancer Genome Atlas Research Network, Integrated genomic characterization of papillary thyroid carcinoma. Cell 159, 676–690 (2014)

    Article  Google Scholar 

  6. S.Y. Nam, J.H. Shin, B.K. Han, E.Y. Ko, E.S. Ko, S.Y. Hahn, J.H. Chung, Preoperative ultrasonographic features of papillary thyroid carcinoma predict biological behavior. J. Clin. Endocrinol. Metab. 98, 1476–1482 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. T. Uematsu, M. Kasami, S. Yuen, Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology 250, 638–647 (2009)

    Article  PubMed  Google Scholar 

  8. J.H. Shin, J.H. Baek, J. Chung, E.J. Ha, J.H. Kim, Y.H. Lee, H.K. Lim, W.J. Moon, D.G. Na, J.S. Park, Y.J. Choi, S.Y. Hahn, S.J. Jeon, S.L. Jung, D.W. Kim, E.K. Kim, J.Y. Kwak, C.Y. Lee, H.J. Lee, J.H. Lee, J.H. Lee, K.H. Lee, S.W. Park, J.Y. Sung, R. Korean society of thyroid, R. Korean society of, ultrasonography diagnosis and imaging-based management of thyroid nodules: revised Korean society of thyroid radiology consensus statement and recommendations. Korean J. Radiol. 17, 370–395 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  9. E.G. Grant, F.N. Tessler, J.K. Hoang, J.E. Langer, M.D. Beland, L.L. Berland, J.J. Cronan, T.S. Desser, M.C. Frates, U.M. Hamper, W.D. Middleton, C.C. Reading, L.M. Scoutt, A.T. Stavros, S.A. Teefey, Thyroid ultrasound reporting lexicon: white paper of the ACR thyroid imaging, reporting and data system (TIRADS) committee. J. Am. Coll. Radiol. 12, 1272–1279 (2015)

    Article  PubMed  Google Scholar 

  10. S. Kim, J. Lee, M.E. Hong, I.G. Do, S.Y. Kang, S.Y. Ha, S.T. Kim, S.H. Park, W.K. Kang, M.G. Choi, J.H. Lee, T.S. Sohn, J.M. Bae, S. Kim, D.H. Kim, K.M. Kim, High-throughput sequencing and copy number variation detection using formalin fixed embedded tissue in metastatic gastric cancer. PLoS ONE 9, e111693 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  11. S. Horn, A. Figl, P.S. Rachakonda, C. Fischer, A. Sucker, A. Gast, S. Kadel, I. Moll, E. Nagore, K. Hemminki, D. Schadendorf, R. Kumar, TERT promoter mutations in familial and sporadic melanoma. Science 339, 959–961 (2013)

    Article  CAS  PubMed  Google Scholar 

  12. K. Barnett, S.W. Mercer, M. Norbury, G. Watt, S. Wyke, B. Guthrie, Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 380, 37–43 (2012)

    Article  PubMed  Google Scholar 

  13. G. Lyratzopoulos, P. Vedsted, H. Singh, Understanding missed opportunities for more timely diagnosis of cancer in symptomatic patients after presentation. Br. J. Cancer 112(Suppl 1), S84–S91 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  14. H.S. Ahn, H.G. Welch, South Korea’s thyroid-cancer “Epidemic”--turning the tide. N. Engl. J. Med. 373, 2389–2390 (2015)

    Article  CAS  PubMed  Google Scholar 

  15. L.J. Esserman, I.M. Thompson Jr., B. Reid, Overdiagnosis and overtreatment in cancer: an opportunity for improvement. J. Am. Med. Assoc. 310, 797–798 (2013)

    Article  CAS  Google Scholar 

  16. H.G. Welch, W.C. Black, Overdiagnosis in cancer. J. Natl. Cancer Inst. 102, 605–613 (2010)

    Article  PubMed  Google Scholar 

  17. M. Xing, A.S. Alzahrani, K.A. Carson, D. Viola, R. Elisei, B. Bendlova, L. Yip, C. Mian, F. Vianello, R.M. Tuttle, E. Robenshtok, J.A. Fagin, E. Puxeddu, L. Fugazzola, A. Czarniecka, B. Jarzab, C.J. O’Neill, M.S. Sywak, A.K. Lam, G. Riesco-Eizaguirre, P. Santisteban, H. Nakayama, R.P. Tufano, S.I. Pai, M.A. Zeiger, W.H. Westra, D.P. Clark, R. Clifton-Bligh, D. Sidransky, P.W. Ladenson, V. Sykorova, Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. J. Am. Med. Assoc. 309, 1493–1501 (2013)

    Article  CAS  Google Scholar 

  18. T.H. Kim, Y.J. Park, J.A. Lim, H.Y. Ahn, E.K. Lee, Y.J. Lee, K.W. Kim, S.K. Hahn, Y.K. Youn, K.H. Kim, B.Y. Cho, J. Park do, The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer 118, 1764–1773 (2012)

    Article  CAS  PubMed  Google Scholar 

  19. J.Y. Kwak, E.K. Kim, W.Y. Chung, H.J. Moon, M.J. Kim, J.R. Choi, Association of BRAFV600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology 253, 854–860 (2009)

    Article  PubMed  Google Scholar 

  20. J. Hwang, J.H. Shin, B.K. Han, E.Y. Ko, S.S. Kang, J.W. Kim, J.H. Chung, Papillary thyroid carcinoma with BRAFV600E mutation: sonographic prediction. Am. J. Roentgenol. 194, W425–W430 (2010)

    Article  Google Scholar 

  21. F.W. Huang, E. Hodis, M.J. Xu, G.V. Kryukov, L. Chin, L.A. Garraway, Highly recurrent TERT promoter mutations in human melanoma. Science 339, 957–959 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Z. Liu, Q. Li, K. Li, L. Chen, W. Li, M. Hou, T. Liu, J. Yang, C. Lindvall, M. Bjorkholm, J. Jia, D. Xu, Telomerase reverse transcriptase promotes epithelial-mesenchymal transition and stem cell-like traits in cancer cells. Oncogene 32, 4203–4213 (2013)

    Article  CAS  PubMed  Google Scholar 

  23. D.G. Na, J.H. Baek, J.Y. Sung, J.H. Kim, J.K. Kim, Y.J. Choi, H. Seo, Thyroid imaging reporting and data system risk stratification of thyroid nodules: categorization based on solidity and echogenicity. Thyroid 26, 562–572 (2016)

    Article  PubMed  Google Scholar 

  24. W.J. Moon, S.L. Jung, J.H. Lee, D.G. Na, J.H. Baek, Y.H. Lee, J. Kim, H.S. Kim, J.S. Byun, D.H. Lee, Benign and malignant thyroid nodules: US differentiation--multicenter retrospective study. Radiology 247, 762–770 (2008)

    Article  PubMed  Google Scholar 

  25. A. Jalaguier-Coudray, J. Thomassin-Piana, Solid masses: what are the underlying histopathological lesions? Diagn. Interv. Imaging 95, 153–168 (2014)

    Article  CAS  PubMed  Google Scholar 

  26. P.M. Lamb, N.M. Perry, S.J. Vinnicombe, C.A. Wells, Correlation between ultrasound characteristics, mammographic findings and histological grade in patients with invasive ductal carcinoma of the breast. Clin. Radiol. 55, 40–44 (2000)

    Article  CAS  PubMed  Google Scholar 

  27. E.K. Kim, C.S. Park, W.Y. Chung, K.K. Oh, D.I. Kim, J.T. Lee, H.S. Yoo, New sonographic criteria for recommending fine-needle aspiration biopsy of nonpalpable solid nodules of the thyroid. Am. J. Roentgenol. 178, 687–691 (2002)

    Article  Google Scholar 

  28. National Comprehensive Cancer Network. Thyroid carcinoma (Version 1.2016). http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed 22 March 2017.

Download references

Funding

This research was supported by Korean Foundation for Cancer Research grant CB-2011-03-02 (to JHC). The funders were not involved in the study design, conduct, or manuscript preparation.

Author information

Author notes

    Authors and Affiliations

    1. Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

      Tae Hyuk Kim, Sun Wook Kim & Jae Hoon Chung

    2. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

      Chang-Seok Ki

    3. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

      Soo Yeon Hahn & Jung Hee Shin

    4. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

      Young Lyun Oh

    5. Department of Medical Education, Sungkyunkwan University School of Medicine, Seoul, Korea

      Hye Won Jang

    Authors
    1. Tae Hyuk Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Chang-Seok Ki
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Soo Yeon Hahn
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Young Lyun Oh
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Hye Won Jang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Sun Wook Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Jae Hoon Chung
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Jung Hee Shin
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Jae Hoon Chung or Jung Hee Shin.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no competing interests.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    Informed consent

    Individual written consent was waived by the committee given the lack of intervention and reporting of data in an individually non-identifiable way.

    Additional information

    Tae Hyuk Kim and Chang-Seok Ki contributed equally to this work.

    Electronic supplementary material

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Kim, T.H., Ki, CS., Hahn, S.Y. et al. Ultrasonographic prediction of highly aggressive telomerase reverse transcriptase (TERT) promoter-mutated papillary thyroid cancer. Endocrine 57, 234–240 (2017). https://doi.org/10.1007/s12020-017-1340-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12020-017-1340-3

    Keywords

    Search

    Navigation