Skip to main content
Top
Published in: Annals of Nuclear Medicine 7/2014

01-08-2014 | Original Article

Predictive role of nontumoral sodium iodide symporter activity and preoperative thyroid characteristics in remission process of thyroid cancer patients

Authors: Nilufer Yildirim-Poyraz, Aylin Yazgan, Elif Ozdemir, Aysegul Gozalan, Mutlay Keskin, Reyhan Ersoy, Seyda Turkolmez, Bekir Cakir

Published in: Annals of Nuclear Medicine | Issue 7/2014

Login to get access

Abstract

Objective

The target of radioiodine ablation therapy (RIAT) after complete tumor removal is the nontumoral remnant tissue. We aimed to evaluate sodium iodide symporter (NIS) expression in nontumoral thyroid tissue in differentiated thyroid cancer (DTC) patients who have complete but delayed structural response (DSR) to RIAT after surgery. Preoperative thyroid characteristics such as volume and nontumoral histology were also investigated for both DSR and its control group as potential predictors of insufficient NIS activity in this study.

Methods

Total of 600 patients with postoperative remnant thyroid tissue and who were in remission after RIAT spontaneously, were included in the study. Patients with positive diagnostic whole body scan (DxWBS) with thyroid bed uptake and stimulated serum Tg level <2 ng/mL at first year visit after initial therapy were defined as DSR group. Immunohistochemical staining of NIS protein was performed on the nontumoral tissue sections from surgery and semi quantified in terms of density and intensity. DSR and its control group were also compared in terms of NIS expression, radioiodine (RAI) uptake on post-therapy scan and preoperative thyroid characteristics.

Results

When compared with the control group, the density and intensity of NIS expression as well as the intensity of RAI uptake were significantly lower in DSR group (p = 0.001). There were also significant differences between groups regarding preoperative thyroid characteristics; i.e. preoperative thyroid volumes were significantly higher and the presence of concurrent benign thyroid disease was significantly more common in DSR group (p = 0.035, p = 0.001). Hashimoto thyroiditis was 8.59 times higher (95 % CI; 2.31–31.96) and multinodular goiter was 7.50 times higher (95 % CI; 1.88–29.91) among DSR group when compared with the control group.

Conclusions

Our findings suggest that insufficient NIS activity in nontumoral thyroid tissue associates with DSR in DTC patients who have postoperative remnant tissue. Preoperative thyroid characteristics such as volume and concomitant benign thyroid disease may have an important role in predicting the complete response time to RIAT in these patients.
Literature
1.
go back to reference 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, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214.PubMedCrossRef 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, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214.PubMedCrossRef
2.
go back to reference Hong CM, Ahn BC, Park JY, Jeong SY, Lee SW, Lee J. Prognostic implications of microscopic involvement of surgical resection margin in patients with differentiated papillary thyroid cancer after high-dose radioactive iodine ablation. Ann Nucl Med. 2012;26:311–8.PubMedCrossRef Hong CM, Ahn BC, Park JY, Jeong SY, Lee SW, Lee J. Prognostic implications of microscopic involvement of surgical resection margin in patients with differentiated papillary thyroid cancer after high-dose radioactive iodine ablation. Ann Nucl Med. 2012;26:311–8.PubMedCrossRef
3.
go back to reference Tuttle RM, Leboeuf R. Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin North Am. 2008;37:419–35.PubMedCrossRef Tuttle RM, Leboeuf R. Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin North Am. 2008;37:419–35.PubMedCrossRef
4.
go back to reference Caminha LS, Momesso DP, Vaisman F, Corbo R, Vaisman M. Long-term follow-up of patients with differentiated thyroid cancer who had negative 131I whole-body scan at first evaluation after treatment. Clin Nucl Med. 2013;38:765–9.PubMedCrossRef Caminha LS, Momesso DP, Vaisman F, Corbo R, Vaisman M. Long-term follow-up of patients with differentiated thyroid cancer who had negative 131I whole-body scan at first evaluation after treatment. Clin Nucl Med. 2013;38:765–9.PubMedCrossRef
5.
go back to reference Castagna MG, Maino F, Cipri C, Belardini V, Theodoropoulou A, Cevenini G, et al. Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur J Endocrinol. 2011;165:441–6.PubMedCrossRef Castagna MG, Maino F, Cipri C, Belardini V, Theodoropoulou A, Cevenini G, et al. Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur J Endocrinol. 2011;165:441–6.PubMedCrossRef
6.
go back to reference Verburg FA, Stokkel MP, Düren C, Verkooijen RB, Mäder U, van Isselt JW, et al. No survival difference after successful (131)I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2010;37:276–83.PubMed Verburg FA, Stokkel MP, Düren C, Verkooijen RB, Mäder U, van Isselt JW, et al. No survival difference after successful (131)I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2010;37:276–83.PubMed
7.
go back to reference Amin A, Badwey A, El-Fatah S. Differentiated thyroid carcinoma: an analysis of 249 patients undergoing therapy and aftercare at a single institution. Clin Nucl Med. 2014;39:142–6.PubMed Amin A, Badwey A, El-Fatah S. Differentiated thyroid carcinoma: an analysis of 249 patients undergoing therapy and aftercare at a single institution. Clin Nucl Med. 2014;39:142–6.PubMed
8.
go back to reference Lim I, Kim SK, Hwang SS, Kim SW, Chung KW, Kang HS, et al. Prognostic implication of thyroglobulin and quantified whole body scan after initial radioiodine therapy on early prediction of ablation and clinical response for the patients with differentiated thyroid cancer. Ann Nucl Med. 2012;26:777–86.PubMedCrossRef Lim I, Kim SK, Hwang SS, Kim SW, Chung KW, Kang HS, et al. Prognostic implication of thyroglobulin and quantified whole body scan after initial radioiodine therapy on early prediction of ablation and clinical response for the patients with differentiated thyroid cancer. Ann Nucl Med. 2012;26:777–86.PubMedCrossRef
9.
go back to reference Vaisman F, Momesso D, Bulzico DA, Pessoa CH, Dias F, Corbo R, et al. Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin Endocrinol (Oxf). 2012;77:132–8.CrossRef Vaisman F, Momesso D, Bulzico DA, Pessoa CH, Dias F, Corbo R, et al. Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin Endocrinol (Oxf). 2012;77:132–8.CrossRef
10.
go back to reference Cherk MH, Francis P, Topliss DJ, Bailey M, Kalff V. Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal. Clin Endocrinol (Oxf). 2012;76:734–40.CrossRef Cherk MH, Francis P, Topliss DJ, Bailey M, Kalff V. Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal. Clin Endocrinol (Oxf). 2012;76:734–40.CrossRef
11.
go back to reference Lim DJ, Kim MH, Kim JH, Kwon HS, Kim SH, et al. Clinical significance of observation without repeated radioiodine therapy in differentiated thyroid carcinoma patients with positive surveillance whole-body scans and negative thyroglobulin. Korean J Intern Med. 2010;25:408–14.PubMedCentralPubMedCrossRef Lim DJ, Kim MH, Kim JH, Kwon HS, Kim SH, et al. Clinical significance of observation without repeated radioiodine therapy in differentiated thyroid carcinoma patients with positive surveillance whole-body scans and negative thyroglobulin. Korean J Intern Med. 2010;25:408–14.PubMedCentralPubMedCrossRef
12.
go back to reference Kim EY, Kim WG, Kim WB, Kim TY, Ryu JS, Gong G, et al. Clinical outcomes of persistent radioiodine uptake in the neck shown by diagnostic whole body scan in patients with differentiated thyroid carcinoma after initial surgery and remnant ablation. Clin Endocrinol (Oxf). 2010;73:257–63. Kim EY, Kim WG, Kim WB, Kim TY, Ryu JS, Gong G, et al. Clinical outcomes of persistent radioiodine uptake in the neck shown by diagnostic whole body scan in patients with differentiated thyroid carcinoma after initial surgery and remnant ablation. Clin Endocrinol (Oxf). 2010;73:257–63.
13.
go back to reference Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol. 2006;155:495–512.PubMedCrossRef Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol. 2006;155:495–512.PubMedCrossRef
14.
go back to reference Smith VE, Read ML, Turnell AS, Watkins RJ, Watkinson JC, Lewy GD, et al. A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer. J Cell Sci. 2009;122:3393–402.PubMedCentralPubMedCrossRef Smith VE, Read ML, Turnell AS, Watkins RJ, Watkinson JC, Lewy GD, et al. A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer. J Cell Sci. 2009;122:3393–402.PubMedCentralPubMedCrossRef
15.
go back to reference Ringel MD, Anderson J, Souza SL, Burch HB, Tambascia M, Shriver CD, et al. Expression of the sodium iodide symporter and thyroglobulin genes are reduced in papillary thyroid cancer. Mod Pathol. 2001;14:289–96.PubMedCrossRef Ringel MD, Anderson J, Souza SL, Burch HB, Tambascia M, Shriver CD, et al. Expression of the sodium iodide symporter and thyroglobulin genes are reduced in papillary thyroid cancer. Mod Pathol. 2001;14:289–96.PubMedCrossRef
16.
go back to reference Sodré AK, Rubio IG, Galrão AL, Knobel M, Tomimori EK, Alves VA, 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.PubMedCrossRef Sodré AK, Rubio IG, Galrão AL, Knobel M, Tomimori EK, Alves VA, 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.PubMedCrossRef
17.
go back to reference Wang S, Liang J, Lin Y, Yao R. Differential expression of the Na(+)/I(-) symporter protein in thyroid cancer and adjacent normal and nodular goiter tissues. Oncol Lett. 2013;5:368–72.PubMedCentralPubMed Wang S, Liang J, Lin Y, Yao R. Differential expression of the Na(+)/I(-) symporter protein in thyroid cancer and adjacent normal and nodular goiter tissues. Oncol Lett. 2013;5:368–72.PubMedCentralPubMed
18.
go back to reference Greene FL, Sobin LH. A worldwide approach to the TNM staging system: collaborative efforts of the AJCC and UICC. J Surg Oncol. 2009;99:269–72.PubMedCrossRef Greene FL, Sobin LH. A worldwide approach to the TNM staging system: collaborative efforts of the AJCC and UICC. J Surg Oncol. 2009;99:269–72.PubMedCrossRef
19.
go back to reference Pacini F, Capezzone M, Elisei R, Ceccarelli C, Taddei D, Pinchera A. Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab. 2002;87:1499–501.PubMedCrossRef Pacini F, Capezzone M, Elisei R, Ceccarelli C, Taddei D, Pinchera A. Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab. 2002;87:1499–501.PubMedCrossRef
20.
go back to reference Rosário PW, Barroso AL, Rezende LL, Padrão EL, Fagundes TA, Reis JS, et al. Outcome of ablation of thyroid remnants with 100 mCi (3.7 GBq) iodine-131 in patients with thyroid cancer. Ann Nucl Med. 2005;19:247–50.PubMedCrossRef Rosário PW, Barroso AL, Rezende LL, Padrão EL, Fagundes TA, Reis JS, et al. Outcome of ablation of thyroid remnants with 100 mCi (3.7 GBq) iodine-131 in patients with thyroid cancer. Ann Nucl Med. 2005;19:247–50.PubMedCrossRef
21.
go back to reference Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol. 2006;155:495–512.PubMedCrossRef Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol. 2006;155:495–512.PubMedCrossRef
22.
go back to reference Suzuki K, Kawashima A, Yoshihara A, Akama T, Sue M, Yoshida A, et al. Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth. J Endocrinol. 2011;209:169–74.PubMedCrossRef Suzuki K, Kawashima A, Yoshihara A, Akama T, Sue M, Yoshida A, et al. Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth. J Endocrinol. 2011;209:169–74.PubMedCrossRef
23.
go back to reference Wagieh SM, El-Refaei SM, Salem SS, Al-Shiekh EA, Al-Ghamdy HA, Al-Juhani NR. Impact of histopathology of non-neoplastic thyroid tissue on ablation outcome in patients with papillary thyroid cancer. Nucl Med Commun. 2011;32:597–604.PubMedCrossRef Wagieh SM, El-Refaei SM, Salem SS, Al-Shiekh EA, Al-Ghamdy HA, Al-Juhani NR. Impact of histopathology of non-neoplastic thyroid tissue on ablation outcome in patients with papillary thyroid cancer. Nucl Med Commun. 2011;32:597–604.PubMedCrossRef
24.
go back to reference Gul K, Dirikoc A, Kiyak G, Ersoy PE, Ugras NS, Ersoy R, et al. The association between thyroid carcinoma and Hashimoto’s thyroiditis: the ultrasonographic and histopathologic characteristics of malignant nodules. Thyroid. 2010;20:873–8.PubMedCrossRef Gul K, Dirikoc A, Kiyak G, Ersoy PE, Ugras NS, Ersoy R, et al. The association between thyroid carcinoma and Hashimoto’s thyroiditis: the ultrasonographic and histopathologic characteristics of malignant nodules. Thyroid. 2010;20:873–8.PubMedCrossRef
25.
go back to reference Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg. 1955;70:291–7.PubMedCrossRef Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg. 1955;70:291–7.PubMedCrossRef
26.
go back to reference Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP. Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery. 1999;126:1070–6.PubMedCrossRef Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP. Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery. 1999;126:1070–6.PubMedCrossRef
27.
go back to reference Konturek A, Barczyński M, Wierzchowski W, Stopa M, Nowak W. Coexistence of papillary thyroid cancer with Hashimoto thyroiditis. Langenbecks Arch Surg. 2013;398:389–94.PubMedCentralPubMedCrossRef Konturek A, Barczyński M, Wierzchowski W, Stopa M, Nowak W. Coexistence of papillary thyroid cancer with Hashimoto thyroiditis. Langenbecks Arch Surg. 2013;398:389–94.PubMedCentralPubMedCrossRef
28.
go back to reference Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, et al. Cloning of the human sodium lodide symporter. Biochem Biophys Res Commun. 1996;226:339–45.PubMedCrossRef Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, et al. Cloning of the human sodium lodide symporter. Biochem Biophys Res Commun. 1996;226:339–45.PubMedCrossRef
29.
go back to reference Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003;24:48–77.PubMedCrossRef Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003;24:48–77.PubMedCrossRef
30.
go back to reference Ferreira AC, Lima LP, Araújo RL, Müller G, Rocha RP, Rosenthal D, et al. Rapid regulation of thyroid sodium-iodide symporter activity by thyrotrophin and iodine. J Endocrinol. 2005;184:69–76.PubMedCrossRef Ferreira AC, Lima LP, Araújo RL, Müller G, Rocha RP, Rosenthal D, et al. Rapid regulation of thyroid sodium-iodide symporter activity by thyrotrophin and iodine. J Endocrinol. 2005;184:69–76.PubMedCrossRef
31.
go back to reference Tuncel M, Aydin D, Yaman E, Tazebay UH, Güç D, Doğan AL, et al. The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake. Cancer Biother Radiopharm. 2007;22:443–9.PubMedCrossRef Tuncel M, Aydin D, Yaman E, Tazebay UH, Güç D, Doğan AL, et al. The comparative effects of gene modulators on thyroid-specific genes and radioiodine uptake. Cancer Biother Radiopharm. 2007;22:443–9.PubMedCrossRef
32.
go back to reference Ozpinar A, Kelestimur F, Songur Y, Can O, Valentin L, Caldwell K, et al. Iodine status in Turkish populations and exposure to iodide uptake inhibitors. PLoS One. 2014;9:e88206.PubMedCentralPubMedCrossRef Ozpinar A, Kelestimur F, Songur Y, Can O, Valentin L, Caldwell K, et al. Iodine status in Turkish populations and exposure to iodide uptake inhibitors. PLoS One. 2014;9:e88206.PubMedCentralPubMedCrossRef
33.
go back to reference Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P, et al. Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. Thyroid. 2004;14:1012–9.PubMedCrossRef Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P, et al. Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. Thyroid. 2004;14:1012–9.PubMedCrossRef
34.
go back to reference Steinmaus C, Miller MD, Howd R. Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001–2002 national health and nutrition examination survey. Environ Health Perspect. 2007;115:1333–8.PubMedCentralPubMedCrossRef Steinmaus C, Miller MD, Howd R. Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001–2002 national health and nutrition examination survey. Environ Health Perspect. 2007;115:1333–8.PubMedCentralPubMedCrossRef
35.
go back to reference Ha W, Suarez DL, Lesch SM. Perchlorate uptake in spinach as related to perchlorate, nitrate, and chloride concentrations in irrigation water. Environ Sci Technol. 2011;45:9363–71.PubMedCrossRef Ha W, Suarez DL, Lesch SM. Perchlorate uptake in spinach as related to perchlorate, nitrate, and chloride concentrations in irrigation water. Environ Sci Technol. 2011;45:9363–71.PubMedCrossRef
36.
37.
go back to reference Cappelli C, Castellano M, Braga M, Gandossi E, Pirola I, De Martino E, et al. Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus microcarcinoma (PMC): a mono-institutional experience. J Surg Oncol. 2007;95:555–60.PubMedCrossRef Cappelli C, Castellano M, Braga M, Gandossi E, Pirola I, De Martino E, et al. Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus microcarcinoma (PMC): a mono-institutional experience. J Surg Oncol. 2007;95:555–60.PubMedCrossRef
38.
go back to reference Küçük NO, Tari P, Tokmak E, Aras G. Treatment for microcarcinoma of the thyroid—clinical experience. Clin Nucl Med. 2007;32:279–81.PubMedCrossRef Küçük NO, Tari P, Tokmak E, Aras G. Treatment for microcarcinoma of the thyroid—clinical experience. Clin Nucl Med. 2007;32:279–81.PubMedCrossRef
Metadata
Title
Predictive role of nontumoral sodium iodide symporter activity and preoperative thyroid characteristics in remission process of thyroid cancer patients
Authors
Nilufer Yildirim-Poyraz
Aylin Yazgan
Elif Ozdemir
Aysegul Gozalan
Mutlay Keskin
Reyhan Ersoy
Seyda Turkolmez
Bekir Cakir
Publication date
01-08-2014
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 7/2014
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-014-0854-5

Other articles of this Issue 7/2014

Annals of Nuclear Medicine 7/2014 Go to the issue