Investigation of Value ofNa＋/I－ Symporter Expression on Diagnosis of Thyroid Carcinoma and Prediction of １31I Therapeutic Effects_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Heng ¹ , ZHU Jingqiang ¹ , TANG Ying ² , LI Zhihui ¹ , WEI Tao ¹

Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Na＋/I－symporter; Thyroid carcinoma; 131I　therapy

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Objective 　To study the clinical value ofNa＋/I－ symporter (NIS) expression on thyroid carcinoma diagnosis and 131I　therapeutic effects prediction.
Methods 　Thirty-one cases of thyroid carcinomas enrolled in this hospital from 1998 to 2006 were included. Using immunohistochemical method, NIS expression location, positive cell staining and expression intensity were observed, which was calculated by immunohistochemical scores (IHS) and NIS expression level was compared between primary and metastatic carcinoma.
Results 　NIS was over-expressed on the basolateral membrane in positive control——Grave disease tissue, and showed no staining in negative control. NIS was expressed in cytoplasm in all 31 primary carcinomas, and IHS was over or equaled to 4 in 80.65% of them. Except for 2 no staining, NIS was expressed in cytoplasm in the rest 28 metastatic carcinomas. NIS expression was related to the pathological type of thyroid carcinoma, the best in PTC, then FTC, and the weakest in fvPTC. NIS expression in metastatic carcinoma was related to that in primary carcinoma.
Conclusion 　NIS is over-expressed in cytoplasm in most thyroid carcinoma, and the iodide uptaking defect is mainly due to its wrong location. It has great potential to be applied in clinic by that it can help with the differential diagnosis of benign and malignant thyroid diseases, especially between FTA and FTC, and that it can help predict the therapeutic effects of 131I　therapy following thyroid operation.

Citation： ZHANG Heng,ZHU Jingqiang,TANG Ying,LI Zhihui,WEI Tao. Investigation of Value ofNa＋/I－ Symporter Expression on Diagnosis of Thyroid Carcinoma and Prediction of １31I Therapeutic Effects. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(5): 554-559. doi: Copy

1.	Dohan O, Baloch Z, Banrevi Z, et al. Rapid communication: predominant intracellular overexpression of the Na(+)/I(-) symporter (NIS) in a large sampling of thyroid cancer cases [J]. J Clin Endocrinol Metab, 2001; 86(6)∶2697.
2.	Saito T, Endo T, Kawaguchi A, et al. Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas [J]. J Clin Invest, 1998; 101(7)∶1296.
3.	Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors [J]. Cancer, 2000; 89(12)∶2637.
4.	Jhiang SM, Cho JY, Ryu KY, et al. An immunohistochemical study ofNa＋/I－ symporter in human thyroid tissues and salivary gland tissues [J]. Endocrinology, 1998; 139(10)∶4416.
5.	Caillou B, Troalen F, Baudin E, et al.Na＋/I－ symporter distribution in human thyroid tissues: an immunohistochemical study [J]. J Clin Endocrinol Metab, 1998; 83(11)∶4102.
6.	Castro MR, Bergert ER, Beito TG, et al. Development of monoclonal antibodies against the human sodium iodide symporter: immunohistochemical characterization of this protein in thyroid cells [J]. J Clin Endocrinol Metab, 1999; 84(8)∶2957.
7.	Castro MR, Bergert ER, Beito TG, et al. Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer [J]. J Endocrinol, 1999; 163(3)∶495.
8.	何友钊，叶观瑞，李美荣，等. B超引导下的细针穿刺活检对甲状腺结节诊断的价值 [J]. 中国普外基础与临床杂志， 2000； 7（1）∶54.
9.	Redman R, Zalaznick H, Mazzaferri EL, et al. The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules [J]. Thyroid, 2006; 16(1)∶55.
10.	Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules [J]. Ann Intern Med, 2005; 142(11)∶926.
11.	Feilchenfeldt J, Totsch M, Sheu SY, et al. Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry [J]. Mod Pathol, 2003; 16(11)∶1117.
12.	Mai KT, Bokhary R, Yazdi HM, et al. Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes [J]. Histopathology, 2002; 40(2)∶133.
13.	姚榛祥. 我国甲状腺外科的展示 [J]. 中国普外基础与临床杂志， 2004； 11（6）∶473.
14.	Tonacchera M, Viacava P, Agretti P, et al. Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein [J]. J Clin Endocrinol Metab, 2002; 87(1)∶352.
15.	Castro MR, Bergert ER, Goellner JR, et al. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake [J]. J Clin Endocrinol Metab, 2001; 86 (11)∶5627.
16.	Min JJ, Chung JK, Lee YJ, et al. Relationship between expression of the sodium/iodide symporter and 1，31I uptake in recurrent lesions of differentiated thyroid carcinoma [J]. Eur J Nucl Med, 2001; 28(5)∶639.
17.	康增寿. 1，31I治疗甲状腺癌 [J]. 中国普外基础与临床杂志， 2006； 13（3）∶252.
18.	Venkataraman GM, Yatin M, Marcinek R, et al. Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to humanNa＋/I－ symporter gene methylation status [J]. J Clin Endocrinol Metab, 1999; 84(7)∶2449.
19.	Zarnegar R, Brunaud L, Kanauchi H, et al. Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor [J]. Surgery, 2002; 132(6)∶984.
20.	Coelho SM, Vaisman M, Carvalho DP. Tumour re-differentiation effect of retinoic acid: a novel therapeutic approach for advanced thyroid cancer [J]. Curr Pharm Des, 2005; 11(19)∶2525.
21.	Robbins RJ, Larson SM, Sinha N, et al. A retrospective revi-ew of the effectiveness of recombinant human TSH as a preparation for radioiodine thyroid remnant ablation [J]. J Nucl Med, 2002; 43(11)∶1482.
22.	Pacini F, Molinaro E, Castagna MG, et al. Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal [J]. J Clin Endocrinol Metab, 2002; 87(9)∶4063.
23.	Luster M, Lippi F, Jarzab B, et al. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review [J]. Endocr Relat Cancer, 2005; 12(1)∶49.
24.	Kogai T, Endo T, Saito T, et al. Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells [J]. Endocrinology, 1997; 138(6)∶2227.
25.	Riedel C, Levy O, Carrasco N. Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin [J]. J Biol Chem, 2001; 276(24)∶21458.
26.	Zidan J, Karen D, Stein M, et al. Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival [J]. Cancer, 2003; 97(5)∶1181.
27.	Passler C, Prager G, Scheuba C, et al. Follicular variant of papillary thyroid carcinoma: a long-term follow-up [J]. Arch Surg, 2003; 138(12)∶1362.
28.	Wittekind Ch, Wagner G. UICC International Union Against Cancer. TNM classification of malignant tumors [M]. 5th Ed. Berlin: Springer， 1997∶128-128.
29.	De Micco C, Vassko V, Henry JF. The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer [J]. Surgery, 1999; 126(6)∶1200.
30.	Chang HY, Lin JD, Chou SC, et al. Clinical presentations and outcomes of surgical treatment of follicular variant of the papillary thyroid carcinomas [J]. Jpn J Clin Oncol, 2006; 36(11)∶688.

1. 　Dohan O, Baloch Z, Banrevi Z, et al. Rapid communication: predominant intracellular overexpression of the Na(+)/I(-) symporter (NIS) in a large sampling of thyroid cancer cases [J]. J Clin Endocrinol Metab, 2001; 86(6)∶2697.
2. 　Saito T, Endo T, Kawaguchi A, et al. Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas [J]. J Clin Invest, 1998; 101(7)∶1296.
3. 　Soslow RA, Dannenberg AJ, Rush D, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors [J]. Cancer, 2000; 89(12)∶2637.
4. 　Jhiang SM, Cho JY, Ryu KY, et al. An immunohistochemical study ofNa＋/I－ symporter in human thyroid tissues and salivary gland tissues [J]. Endocrinology, 1998; 139(10)∶4416.
5. 　Caillou B, Troalen F, Baudin E, et al.Na＋/I－ symporter distribution in human thyroid tissues: an immunohistochemical study [J]. J Clin Endocrinol Metab, 1998; 83(11)∶4102.
6. 　Castro MR, Bergert ER, Beito TG, et al. Development of monoclonal antibodies against the human sodium iodide symporter: immunohistochemical characterization of this protein in thyroid cells [J]. J Clin Endocrinol Metab, 1999; 84(8)∶2957.
7. 　Castro MR, Bergert ER, Beito TG, et al. Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer [J]. J Endocrinol, 1999; 163(3)∶495.
8. 　何友钊，叶观瑞，李美荣，等. B超引导下的细针穿刺活检对甲状腺结节诊断的价值 [J]. 中国普外基础与临床杂志， 2000； 7（1）∶54.
9. 　Redman R, Zalaznick H, Mazzaferri EL, et al. The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules [J]. Thyroid, 2006; 16(1)∶55.
10. 　Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules [J]. Ann Intern Med, 2005; 142(11)∶926.
11. 　Feilchenfeldt J, Totsch M, Sheu SY, et al. Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry [J]. Mod Pathol, 2003; 16(11)∶1117.
12. 　Mai KT, Bokhary R, Yazdi HM, et al. Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes [J]. Histopathology, 2002; 40(2)∶133.
13. 　姚榛祥. 我国甲状腺外科的展示 [J]. 中国普外基础与临床杂志， 2004； 11（6）∶473.
14. 　Tonacchera M, Viacava P, Agretti P, et al. Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein [J]. J Clin Endocrinol Metab, 2002; 87(1)∶352.
15. 　Castro MR, Bergert ER, Goellner JR, et al. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake [J]. J Clin Endocrinol Metab, 2001; 86 (11)∶5627.
16. 　Min JJ, Chung JK, Lee YJ, et al. Relationship between expression of the sodium/iodide symporter and 1，31I uptake in recurrent lesions of differentiated thyroid carcinoma [J]. Eur J Nucl Med, 2001; 28(5)∶639.
17. 　康增寿. 1，31I治疗甲状腺癌 [J]. 中国普外基础与临床杂志， 2006； 13（3）∶252.
18. 　Venkataraman GM, Yatin M, Marcinek R, et al. Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to humanNa＋/I－ symporter gene methylation status [J]. J Clin Endocrinol Metab, 1999; 84(7)∶2449.
19. 　Zarnegar R, Brunaud L, Kanauchi H, et al. Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor [J]. Surgery, 2002; 132(6)∶984.
20. 　Coelho SM, Vaisman M, Carvalho DP. Tumour re-differentiation effect of retinoic acid: a novel therapeutic approach for advanced thyroid cancer [J]. Curr Pharm Des, 2005; 11(19)∶2525.
21. 　Robbins RJ, Larson SM, Sinha N, et al. A retrospective revi-ew of the effectiveness of recombinant human TSH as a preparation for radioiodine thyroid remnant ablation [J]. J Nucl Med, 2002; 43(11)∶1482.
22. 　Pacini F, Molinaro E, Castagna MG, et al. Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal [J]. J Clin Endocrinol Metab, 2002; 87(9)∶4063.
23. 　Luster M, Lippi F, Jarzab B, et al. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review [J]. Endocr Relat Cancer, 2005; 12(1)∶49.
24. 　Kogai T, Endo T, Saito T, et al. Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells [J]. Endocrinology, 1997; 138(6)∶2227.
25. 　Riedel C, Levy O, Carrasco N. Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin [J]. J Biol Chem, 2001; 276(24)∶21458.
26. 　Zidan J, Karen D, Stein M, et al. Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival [J]. Cancer, 2003; 97(5)∶1181.
27. 　Passler C, Prager G, Scheuba C, et al. Follicular variant of papillary thyroid carcinoma: a long-term follow-up [J]. Arch Surg, 2003; 138(12)∶1362.
28. 　Wittekind Ch, Wagner G. UICC International Union Against Cancer. TNM classification of malignant tumors [M]. 5th Ed. Berlin: Springer， 1997∶128-128.
29. 　De Micco C, Vassko V, Henry JF. The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer [J]. Surgery, 1999; 126(6)∶1200.
30. 　Chang HY, Lin JD, Chou SC, et al. Clinical presentations and outcomes of surgical treatment of follicular variant of the papillary thyroid carcinomas [J]. Jpn J Clin Oncol, 2006; 36(11)∶688.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Investigation of Value ofNa＋/I－ Symporter Expression on Diagnosis of Thyroid Carcinoma and Prediction of １31I Therapeutic Effects

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