NIS蛋白表達對甲狀腺癌診斷及131I療效預測的相關性研究_《中國普外基礎與臨床雜志》

作者：

張恒 ¹ , 朱精強 ¹ , 唐穎 ² , 李志輝 ¹ , 魏濤 ¹

1.四川大學華西醫院普外科(成都610041);;
2.四川大學華西醫院病理科;

關鍵詞：

鈉碘同向轉運體甲狀腺癌 131碘治療

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目的　探討鈉碘同向轉運體（Na＋/I－ symporter,NIS）蛋白表達在甲狀腺癌診斷及術后131I治療效果預測方面的臨床應用價值。
方法　選取我院1998～2006年病理診斷為甲狀腺癌的31例患者，采用免疫組化法檢測NIS蛋白在細胞中的表達部位、陽性細胞數及表達強度，并以免疫組化評分（immunohistochemical scores,IHS）表示，研究在不同病理類型甲狀腺癌原發灶及轉移灶中NIS蛋白的表達情況。
結果　陽性對照Grave病甲狀腺組織中NIS蛋白呈強表達，定位于甲狀腺濾泡上皮細胞基底部質膜或周邊質膜；陰性對照不表達。31例甲狀腺癌原發灶細胞胞漿均為NIS陽性表達，其中80.65%的患者IHS≥4分； 30例轉移灶中，除2例不表達外，其余為胞漿陽性。轉移灶與原發灶中NIS蛋白表達具有正相關；甲狀腺癌原發灶NIS蛋白表達與甲狀腺癌病理類型有關，在乳頭狀癌（PTC）中最強，濾泡狀腺癌（FTC）中次之，濾泡型乳頭狀癌（fvPTC）中表達較弱。
結論　NIS蛋白表達在甲狀腺癌中主要定位于胞漿，其攝碘障礙可能主要是錯誤定位的結果。NIS蛋白在不同甲狀腺疾病組織中的表達差異有助于甲狀腺良、惡性疾病，尤其是FTC與濾泡型腺瘤的鑒別診斷，也有助于不同病理類型甲狀腺癌的鑒別。原發灶NIS蛋白表達水平對預測轉移灶131I療效有幫助，NIS蛋白的免疫組化檢測有廣闊的臨床應用前景。

引用本文： 張恒,朱精強,唐穎,李志輝,魏濤. NIS蛋白表達對甲狀腺癌診斷及131I療效預測的相關性研究. 中國普外基礎與臨床雜志, 2007, 14(5): 554-559. doi: 復制

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.	何友釗，葉觀瑞，李美榮，等. B超引導下的細針穿刺活檢對甲狀腺結節診斷的價值 [J]. 中國普外基礎與臨床雜志， 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. 我國甲狀腺外科的展示 [J]. 中國普外基礎與臨床雜志， 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.	康增壽. 1，31I治療甲狀腺癌 [J]. 中國普外基礎與臨床雜志， 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. 　何友釗，葉觀瑞，李美榮，等. B超引導下的細針穿刺活檢對甲狀腺結節診斷的價值 [J]. 中國普外基礎與臨床雜志， 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. 我國甲狀腺外科的展示 [J]. 中國普外基礎與臨床雜志， 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. 　康增壽. 1，31I治療甲狀腺癌 [J]. 中國普外基礎與臨床雜志， 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.

《中國普外基礎與臨床雜志》

NIS蛋白表達對甲狀腺癌診斷及131I療效預測的相關性研究

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《中國普外基礎與臨床雜志》

NIS蛋白表達對甲狀腺癌診斷及131I療效預測的相關性研究

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