Annals of Surgical Oncology

, Volume 19, Issue 3, pp 990–995 | Cite as

Expression of Sodium–Iodide Symporter and TSH Receptor in Subclinical Metastatic Lymph Nodes of Papillary Thyroid Microcarcinoma

  • Yoon Kyoung So
  • Young-Ik Son
  • Chung-Hwan Baek
  • Han-Sin Jeong
  • Man Ki Chung
  • Young-Hyeh Ko
Endocrine Tumors



The clinical significance of the subclinical lymph node (LN) metastasis in clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) has been debated. We investigated the expression of sodium–iodide symporter (NIS) and thyroid-stimulating hormone receptor (TSHR) in the subclinical metastatic LNs of PTMC, which are crucial prerequisites for the response to radioactive iodine treatment.


Among 149 consecutive patients who received total thyroidectomy in conjunction with prophylactic central neck dissection for cN0 PTMC from October 2005 to December 2007, 20 who had single PTMC and subclinical LN metastasis (cN0, pN1, single PTMC) were included. Immunohistochemical staining was performed with anti-human NIS antibody and anti-human TSHR antibody in 20 primary tumors and 52 metastatic LNs.


NIS and TSHR expression was detected in 19 (95%) and 18 (90%) of 20 PTMCs, respectively. NIS and TSHR expression were also detected in 50 (96.2%) and 39 (75%) of 52 metastatic LNs, respectively. In 85% of patients, the presence of NIS expression in primary PTMCs was concordant with that in corresponding metastatic LNs. Intensities of NIS and TSHR expression were diverse. In 6 of 12 cases of multiple metastatic LNs, the metastatic LNs showed heterogeneous intensities of NIS expression.


The presence of NIS and TSHR expression was observed with high frequency in both PTMCs and corresponding subclinical metastatic LNs. However, the intensity of NIS and TSHR expression was diverse. Multiple metastatic LNs from single primary tumor focus could have heterogeneous intensity of NIS expression.


Papillary Thyroid Carcinoma Total Thyroidectomy Central Neck Dissection Papillary Thyroid Microcarcinoma Prophylactic Central Neck Dissection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by Health and Medical Technology R&D Program, Korea (grant A090740).


  1. 1.
    Ito Y, Tomoda C, Uruno T, et al. Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid. World J Surg. 2006;30:91–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Stulak JM, Grant CS, Farley DR, et al. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg. 2006;141:489–94.PubMedCrossRefGoogle Scholar
  3. 3.
    So YK, Son YI, Hong SD, et al. Subclinical lymph node metastasis in papillary thyroid microcarcinoma: a study of 551 resections. Surgery. 2010;148:526–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214.PubMedCrossRefGoogle Scholar
  5. 5.
    Besic N, Pilko G, Petric R, Hocevar M, Zgajnar J. Papillary thyroid microcarcinoma: prognostic factors and treatment. J Surg Oncol. 2008;97:221–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality. Cancer. 2003;98:31–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Hay ID, Hutchinson ME, Gonzalez-Losada T, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery. 2008;144:980–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;237:399–407.PubMedGoogle Scholar
  9. 9.
    Spitzweg C, Morris JC. The sodium iodide symporter: its pathophysiological and therapeutic implications. Clin Endocrinol (Oxf). 2002;57:559–74.CrossRefGoogle Scholar
  10. 10.
    Kogai T, Endo T, Saito T, Miyazaki A, Kawaguchi A, Onaya T. Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells. Endocrinology. 1997;138:2227–32.PubMedCrossRefGoogle Scholar
  11. 11.
    Riedel C, Levy O, Carrasco N. Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem. 2001;276:21458–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Carty SE, Cooper DS, Doherty GM, et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid. 2009;19:1153–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lim YC, Choi EC, Yoon YH, Kim EH, Koo BS. Central lymph node metastases in unilateral papillary thyroid microcarcinoma. Br J Surg. 2009;96:253–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Roh JL, Park JY, Park CI. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg. 2007;245:604–10.PubMedCrossRefGoogle Scholar
  15. 15.
    So YK, Seo MY, Son YI. Prophylactic central lymph node dissection for clinically node-negative papillary thyroid microcarcinoma: influence on serum thyroglobulin level, recurrence rate, and postoperative complications. Surgery. 2011.Google Scholar
  16. 16.
    Arturi F, Russo D, Giuffrida D, Schlumberger M, Filetti S. Sodium-iodide symporter (NIS) gene expression in lymph-node metastases of papillary thyroid carcinomas. Eur J Endocrinol. 2000;143:623–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Castro MR, Bergert ER, Goellner JR, Hay ID, Morris JC. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab. 2001;86:5627–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Jung YH, Hah JH, Sung MW, Kim KH, Cho SY, Jeon YK. Reciprocal immunohistochemical expression of sodium/iodide symporter and hexokinase I in primary thyroid tumors with synchronous cervical metastasis. Laryngoscope. 2009;119:541–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Min JJ, Chung JK, Lee YJ, et al. Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma. Eur J Nucl Med. 2001;28:639–45.PubMedCrossRefGoogle Scholar
  20. 20.
    Patel A, Jhiang S, Dogra S, et al. Differentiated thyroid carcinoma that express sodium–iodide symporter have a lower risk of recurrence for children and adolescents. Pediatr Res. 2002;52:737–44.PubMedGoogle Scholar
  21. 21.
    Saito T, Endo T, Kawaguchi A, et al. Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas. J Clin Invest. 1998;101:1296–300.PubMedCrossRefGoogle Scholar
  22. 22.
    Sodre AK, Rubio IG, Galrao AL, et al. Association of low sodium–iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining. J Clin Endocrinol Metab. 2008;93:4141–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Oler G, Ebina KN, Michaluart P Jr, Kimura ET, Cerutti J. Investigation of BRAF mutation in a series of papillary thyroid carcinoma and matched-lymph node metastasis reveals a new mutation in metastasis. Clin Endocrinol (Oxf). 2005;62:509–11.CrossRefGoogle Scholar
  24. 24.
    Vasko V, Hu S, Wu G, et al. High prevalence and possible de novo formation of BRAF mutation in metastasized papillary thyroid cancer in lymph nodes. J Clin Endocrinol Metab. 2005;90:5265–9.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Yoon Kyoung So
    • 1
  • Young-Ik Son
    • 2
  • Chung-Hwan Baek
    • 2
  • Han-Sin Jeong
    • 2
  • Man Ki Chung
    • 2
  • Young-Hyeh Ko
    • 3
  1. 1.Department of Otorhinolaryngology-Head and Neck SurgeryInje University College of Medicine, Haeundae Paik HospitalPusanKorea
  2. 2.Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  3. 3.Department of Pathology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea

Personalised recommendations