Castro M R, Bergert E R, Goellner J R, Hay I D, Morris J C
Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
J Clin Endocrinol Metab. 2001 Nov;86(11):5627-32. doi: 10.1210/jcem.86.11.8048.
The ability of thyroid cancers to concentrate radioiodine (RAI) is dependent, in part, upon the expression and functional integrity of the sodium iodide symporter (NIS). However, some differentiated thyroid carcinomas (DTCs) and most undifferentiated thyroid carcinomas lack the ability to concentrate iodide and are thereby insensitive to 131I therapy. Variation of NIS protein expression may be an important factor in this behavior. We wished to determine whether NIS protein expression in primary DTC tumors correlated with the subsequent RAI uptake by metastatic lesions in the same patients. We obtained paraffin-embedded tissue specimens from 60 patients with metastatic thyroid cancer who had undergone total or near-total thyroidectomy at the Mayo Clinic for DTC and had known presence or absence of RAI uptake in their tumor deposits determined by total body scanning after thyroid hormone withdrawal. Tissue sections from the primary intrathyroidal tumors were subjected to immunostaining (IS) using a monoclonal antibody against human NIS. Slides were subsequently examined for specific IS by two independent reviewers. For each patient, whole body scan (WBS) uptake was recorded, and correlation between results of IS and WBS was analyzed. Of 43 patients with a positive WBS, 37 also had positive IS of their tumors. In six patients with negative IS, a positive WBS was documented, and in three of these cases TSH at the time of surgery was less than 0.3 mIU/liter. Of the 17 patients with negative WBS, 10 were also negative on IS. Positive IS accurately predicted a positive scan in our study in 84% of cases; the ability of the IS to detect all cases with a positive scan was 86%, and it increased to 90% when patients who were receiving thyroid hormone therapy at the time of surgery were excluded from the analysis. Overall, the results of our retrospective study suggest that NIS IS of the thyroidal primary tumor in patients with papillary and follicular thyroid cancers has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer with respect to iodine trapping and concentration. Our findings require confirmation in prospective studies to more accurately determine the predictive ability of the test and its role in the postoperative management of patients with DTC. If confirmed, NIS IS of DTC primary lesions may prove useful in the management of patients with known or suspected metastatic thyroid cancer.
甲状腺癌摄取放射性碘（RAI）的能力部分取决于钠碘同向转运体（NIS）的表达及功能完整性。然而，一些分化型甲状腺癌（DTC）和大多数未分化型甲状腺癌缺乏摄取碘的能力，因此对131I治疗不敏感。NIS蛋白表达的变化可能是导致这种情况的一个重要因素。我们希望确定原发性DTC肿瘤中NIS蛋白表达是否与同一患者转移灶随后的RAI摄取相关。我们从60例转移性甲状腺癌患者中获取石蜡包埋组织标本，这些患者在梅奥诊所因DTC接受了全甲状腺切除或近全甲状腺切除，且已知在停用甲状腺激素后通过全身扫描确定其肿瘤灶有无RAI摄取。取自甲状腺内原发性肿瘤的组织切片用抗人NIS单克隆抗体进行免疫染色（IS）。随后由两名独立的审阅者检查玻片的特异性IS。记录每位患者的全身扫描（WBS）摄取情况，并分析IS结果与WBS结果之间的相关性。在43例WBS阳性的患者中，37例肿瘤的IS也呈阳性。在6例IS阴性的患者中，记录到WBS阳性，其中3例手术时促甲状腺激素（TSH）低于0.3 mIU/升。在17例WBS阴性的患者中，10例的IS也为阴性。在我们的研究中，阳性IS在84%的病例中准确预测了阳性扫描；IS检测所有阳性扫描病例的能力为86%，当排除手术时接受甲状腺激素治疗的患者进行分析时，这一能力提高到90%。总体而言，我们的回顾性研究结果表明，对于乳头状和滤泡状甲状腺癌患者，甲状腺原发性肿瘤的NIS IS在预测转移性和复发性癌后续病灶的碘捕获和浓聚行为方面具有较强的能力。我们的研究结果需要在前瞻性研究中得到证实，以便更准确地确定该检测的预测能力及其在DTC患者术后管理中的作用。如果得到证实，DTC原发性病灶的NIS IS可能在已知或疑似转移性甲状腺癌患者的管理中发挥作用。
