Tumor Biology

, Volume 35, Issue 9, pp 8559–8564 | Cite as

Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma

  • Xi Wei
  • Ying Li
  • Sheng Zhang
  • Ming Gao
Research Article


The aim of our study was to find a specific imaging (contrast-enhanced ultrasound, CEUS) to detect extracapsular extension and cervical lymph node metastases (ECE-LNM) that associated with BRAF protein expression in papillary thyroid carcinoma (PTC). Preoperative utrasonography (US) or CEUS was performed in the diagnosis of extracapsular extension (ECE) in 317 patients with 369 PTC. BRAF protein status was tested on the primary tumor and lymph node involvement. The diagnostic accuracy of CEUS and US was evaluated after thyroid surgery. The association between CEUS and BRAF expression were then analyzed to investigate the diagnostic value of ECE-LNM in PTC. The sensitivity and specificity of CEUS were higher than those in US in the diagnosis of ECE in patients with PTC (91.1, 86.5 vs 49, 55 %). BRAF protein overexpression were significantly associated with ECE (P = 0.0003) and lymph node metastasis (LNM) positive cases (P = 0.0014). The results of CEUS, not US, have a significant correlation with BRAF expression status in PTC samples (P < 0.0001). Associated with BRAF protein expression status, the routine preoperative CEUS could have a good value in the diagnosis of ECE-LNM in PTC and facilitate a surgeon to improve further clinical management.


Contrast-enhanced ultrasound BRAF Extracapsular extension Cervical lymph node metastases Papillary thyroid cancer 


Conflict of interest



  1. 1.
    Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Qian B, Chen K, He M, Dong SF, Han HW, Lei L, et al. The survey on thyroid carcinoma incidence in urban district of Tianjin. Chin J Clin Oncol. 2005;32:218–21. Article in Chinese.Google Scholar
  3. 3.
    Mirallie E, Visset J, Sagan C, Hamy A, Le Bodic MF, Paineau J. Localization of cervical node metastasis of papillary thyroid carcinoma. World J Surg. 1999;23:970–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Mimura T, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optical strategy for neck dissection. Ann Surg. 2003;237:399–407.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Pereira JA, Jimeno J, Miquel J, Iglesias M. Munne’ A, Sancho JJ, Sitges-Serra A. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery. 2005;138:1095–100.CrossRefPubMedGoogle Scholar
  6. 6.
    Mazzaferri EL, Kloos RT. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001;86:1447–63.CrossRefPubMedGoogle Scholar
  7. 7.
    Hay ID, Bergstralh EJ, Grant CS, McIver B, Thompson GB, van Heerden JA, et al. Impact of primary surgery on outcome in 300 patients with pathologic tumor-node-metastasis stage III papillary thyroid carcinoma treated at one institution from 1940 through 1989. Surgery. 1999;126:1173–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Tsang RW, Brierley JD, Simpson WJ, Panzarella T, Gospodarowicz MK, Sut-cliffe SB. The effects of surgery, radioiodine, and external radiation therapy on the clinical outcome of patients with differentiated thyroid carcinoma. Cancer. 1998;82:375–88.CrossRefPubMedGoogle Scholar
  9. 9.
    Kouvaraki MA, Shapiro SE, Fornage BD, Edeiken-Monro BS, Sherman SI, Vassilopoulou-Sellin R, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery. 2003;134:946–54.CrossRefPubMedGoogle Scholar
  10. 10.
    Ishigaki S, Shimamoto K, Satake H, Sawaki A, Itoh S, Ikeda M, et al. Multi-slice CT of thyroid nodules: comparison with ultrasonography. Radiat Med. 2004;22:346–53.PubMedGoogle Scholar
  11. 11.
    King AD, Ahuja AT, To EW, Tse GM, Metreweli C. Staging papillary carcinoma of the thyroid: magnetic resonance imaging vs ultrasound of the neck. Clin Radiol. 2000;55:222–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Shimamoto K, Satake H, Sawaki A, Ishigaki T, Funahashi H, Imai T. Preoperative staging of thyroid papillary carcinoma with ultrasonography. Eur J Radiol. 1998;29:4–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Dănilă M, Sporea I, Sirli R, Popescu A, Sendroiu M, Martie A. The role of contrast enhanced ultrasound (CEUS) in the assessment of liver nodules in patients with cirrhosis. Med Ultrason. 2010;12:145–9.PubMedGoogle Scholar
  14. 14.
    Agha A, Jung EM, Janke M, Hornung M, Georgieva M, Schlitt HJ, et al. Preoperative diagnosis of thyroid adenomas using high resolution contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc. 2013;55:403–9.PubMedGoogle Scholar
  15. 15.
    Ma JJ, Ding H, Xu BH, Xu C, Song LJ, Huang BJ, et al. Diagnostic performances of various gray-scale, color Doppler, and contrast-enhanced ultrasonography findings in predicting malignant thyroid nodules. Thyroid. 2014;24:355–63.CrossRefPubMedGoogle Scholar
  16. 16.
    Rossi ED, Martini M, Capodimonti S, Lombardi CP, Pontecorvi A, Vellone VG, et al. BRAF (V600E) mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma. Cancer Cytopathol. 2013;121:291–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88:4393–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005;90:6373–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Kabaker AS, Tublin ME, Nikiforov YE, Armstrong MJ, Hodak SP, Stang MT, et al. Suspicious ultrasound characteristics predict BRAF V600E-positive papillary thyroid carcinoma. Thyroid. 2012;22:585–9.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Patron V, Hitier M, Bedfert C, Métreau A, Dugué A, Jegoux F. Predictive factors for lateral occult lymph node metastasis in papillary thyroid carcinoma. Eur Arch Otorhinolaryngol. 2013;270:2095–100.CrossRefPubMedGoogle Scholar
  21. 21.
    Kim KE, Kim EK, Yoon JH, Han KH, Moon HJ, Kwak JY. Preoperative prediction of central lymph node metastasis in thyroid papillary microcarcinoma using clinicopathologic and sonographic features. World J Surg. 2013;37:385–91.CrossRefPubMedGoogle Scholar
  22. 22.
    Joo JY, Park JY, Yoon YH, Choi B, Kim JM, Jo YS, et al. Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoperative braf analysis using fine-needle aspiration biopsy: a prospective study. J Clin Endocrinol Metab. 2012;97:3996–4003.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee YS, Lim YS, Lee JC, Wang SG, Kim IJ, Son SM, et al. Nodal status of central lymph nodes as a negative prognostic factor forpapillary thyroid carcinoma. J Surg Oncol. 2013;107:777–82.CrossRefPubMedGoogle Scholar
  24. 24.
    Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart JM, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 2005;90:5723–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Ito Y, Hirokawa M, Uruno T, Kihara M, Higashiyama T, Takamura Y, et al. Biological behavior and prognosis of encapsulated papillary carcinoma of the thyroid: experience of a Japanese hospital for thyroid care. World J Surg. 2008;32:1789–94.CrossRefPubMedGoogle Scholar
  26. 26.
    Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab. 2002;87:1941–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Feng L, Li M, Zhang QP, Piao ZA, Wang ZH, Lv S. Utility of BRAF protein overexpression in predicting the metastasis potential of papillary thyroid carcinoma. Oncol Lett. 2011;2:59–63.PubMedCentralPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Diagnostic and Therapeutic UltrasonographyTianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and TherapyTianjinChina
  2. 2.The Third Department of Breast CancerTianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and TherapyTianjinChina
  3. 3.Department of Thyroid and Cervical TumorTianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and TherapyTianjinChina

Personalised recommendations