Low expression of sodium iodide symporter identifies aggressive thyroid tumors
Introduction
Appropriate therapy in differentiated carcinoma patients offers a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery followed by radioiodine ablation of residual normal or neoplastic cells is of proven efficacy. Subsequently, patients are managed on levothyroxine to reduce serum levels of the pituitary hormone thyrotropin (TSH) aiming to minimize the growth of any residual tumor. Whole body radioiodine scanning (WBS) and measurement of serum thyroglobulin (Tg) concentration are used to monitor patients. Recurrence develops in 20–40% of patients over decades of follow-up and as well as metastases, are confirmed and treated with radioiodine again [1].
Sodium iodide symporter (NIS) is a membrane glycoprotein that actively mediates iodide uptake on the basolateral membrane of thyroid follicular cells. Because NIS forms the molecular basis for using radioiodine as scintigraphic imaging and therapeutic agent for tissues showing iodine uptake, many investigators have focused on NIS expression and function in thyroid cancer. Indeed, a decreased ability to concentrate radioiodine is frequently detected in most differentiated thyroid carcinomas, with wide variability from one tumor to another. Absolute absence of iodide uptake is found in almost one-third of cases [2]. In addition, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumor grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumors may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy [1].
In human thyroid carcinomas, expression of the NIS transcript was detectable, even though at low levels, in most of the tumors examined but extremely reduced or even absent in some of them [3], [4], [5]. Indeed, a recent retrospective immunohistochemical analysis of NIS expression in metastatic differentiated thyroid cancer showed a fair correlation with radioiodine uptake suggesting that NIS expression in the thyroidal primary tumor has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer regarding iodine trapping and concentration in patients with papillary and follicular thyroid cancers [6]. To investigate this possibility, we carried out a prospective case-control study based on the quantitative evaluation of NIS mRNA relative expression levels in the primary thyroid tumor.
Section snippets
Subjects
The Ethics Committee of the University Hospital—School of Medicine of the State University of Campinas, approved this study and informed written consent was obtained from patients that were consecutively referred to our service because of thyroid nodules. After a fine-needle aspiration biopsy that revealed malignant or suspicious cells, the patients were submitted to a total or near-total thyroidectomy. Thyroid tissue samples from both the index nodule and roughly normal-appearing thyroid
Results
Table 1 summarizes clinical, pathological and follow-up data of the 17 differentiated thyroid carcinoma patients. Using tumor staging at diagnosis and the follow-up data, we could characterize a group A of five PC patients with aggressive carcinomas, that presented local recurrence and/or distant metastasis, in contrast with other six patients (group B) that were disease-free at the end of the period of 24 months observation. The remaining three patients are still under observation and
Discussion
Because most differentiated thyroid carcinomas have an excellent prognosis, some authors have been claiming that these patients are suffering from overtreatment, i.e. total thyroidectomy and ablation of remnants with high doses of radioiodine [9]. Indeed, many surveys reveal relative survival rates up to 93–98% and 85–92% for papillary and follicular carcinoma, respectively [10], [11]. However, the remaining subset of patients develops early recurrence and/or distant metastasis, contributing to
Conclusions
Because radioiodine represents a major diagnostic and therapeutic tool for the management of differentiated thyroid cancer patients, the presence and functional integrity of NIS are prerequisites for iodine concentration. Our results indicate that quantification of NIS mRNA levels could be added to the classic prognostic factors currently used to predict the outcome of patients with differentiated thyroid carcinomas. These data also suggest that patients with primary thyroid tumors with low NIS
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