Expression of the apical iodide transporter in human thyroid tissues: a comparison study with other iodide transporters.

Iodide transport by thyrocytes involves two transporters, namely the Na(+)/I (-) symporter located at the basolateral pole and possibly pendrin in the apical membranes of the cell. Recently, we identified a human gene and its protein product, designated hAIT, as a putative new transporter involved in iodide transfer across the apical membrane of thyrocytes. In the present report, we analyzed both hAIT gene and protein expressions in a large series of benign and malignant human thyroid tissues. Using immunohistochemistry, hAIT staining was detected in normal thyroid tissue in about 10% of follicles; in positive follicles, 10-40% of thyrocytes, mostly the tall cells, were stained. In thyroid tissues obtained from patients with Graves' disease and toxic adenomas, hAIT mRNA and protein levels were similar to those found in normal tissue. In hypofunctioning adenomas, hAIT mRNA levels were slightly decreased, and apical iodide transporter (AIT) immunostaining was similar to that observed in normal thyroid tissue. AIT staining was stronger in Hürthle cell adenomas and in microfollicular adenomas. In thyroid carcinomas, the mean and median hAIT mRNA levels were significantly decreased. Expression of AIT protein was undetectable in most papillary carcinomas and was weak but detectable in most follicular carcinomas; it was negative in anaplastic carcinomas.

Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue.

UNLABELLED: The high sensitivity of the thyroid gland to the carcinogenic effects of radiation during childhood contrasts with the absence of demonstrable carcinogenic effects of radiation in adults. To better understand these age-related variations, we studied follicular morphometry, functional status, and proliferative activity in 31 thyroid glands removed from relatives of medullary thyroid carcinoma patients, with ages ranging from 3 to 39 y. METHODS: The mean follicular diameter (MFD) was estimated, and immunohistochemistry was performed with antibodies directed to molecules involved in iodide transport (Na(+)/I(-) symporter [NIS], pendrin, and apical iodide transporter), in organification (thyroperoxidase [TPO] and Duox), in cell cycle and growth (Ki-67, cyclin A and D1, and galectin-3), and in angiogenesis (vascular endothelial growth factor and nitric oxide synthase III [NOSIII]). RESULTS: Compared with older patients, patients who were < or =12 y old had a smaller MFD (P < 0.001) and more frequently positive NIS, pendrin, and Duox (P < 0.01). Proliferation rate as indicated by cyclin A expression was also higher in patients < 12 y (P < 0.01) but peaked at the time of puberty. Staining for NIS, pendrin, TPO, Duox, and NOSIII was stronger in thyroid glands with a smaller MFD (P < 0.001). On multiple tests adjusted for age and thyroid mass, TPO, Duox, and NOSIII remained significantly correlated to MFD (P < 0.001), whereas staining for NIS and pendrin did not. This finding suggests that NIS and pendrin expression is related mainly to the age of the patient. CONCLUSION: Smaller follicles with a higher expression of proteins involved in iodide metabolism were found in younger children. In cases of radioiodine contamination in children, the result will be a higher radioactive concentration and, hence, higher radiation doses. This event may induce the development of thyroid cancer under conditions of accelerated proliferation, as evidenced at puberty.

Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.

UNLABELLED: A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01). IN CONCLUSION: 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.

Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma.

Serum thyroglobulin (Tg) is a reliable marker for detecting recurrent and persistent disease during the follow-up of patients with papillary and follicular thyroid carcinoma. The goal of this study was to assess the relationship between the serum Tg level measured after thyroid hormone withdrawal and the tumor mass in thyroid cancer patients who underwent surgery with the use of an intraoperative probe for lymph node metastases with (131)I uptake. Patients were classified into one of three groups according to the Tg level: undetectable (n = 18); 1-10 ng/mL (n = 21); and greater than 10 ng/mL (n = 33). The main clinical characteristics and the extent of the disease at the time of initial treatment were similar in these three groups. Lymph node metastases were found in 13 of the 18 patients with undetectable Tg level. Eight patients had persistent foci of uptake after surgery that were located behind the sterno-clavicular joint in six patients. The number of metastatic lymph nodes and their total surface (in mm(2)) or their total volume (in mm(3)) were significantly linked with serum Tg/thyrotropin [TSH] level (p = 0.002 and p < 0.0001, respectively). For a given metastatic surface or volume, the serum Tg/TSH value was no longer linked with the number of metastatic lymph nodes (p = 0.32), suggesting that the total surface or total volume is the characteristic that best summarizes the influence of the disease on the serum Tg/TSH level. In conclusion, patients with higher serum Tg levels tend to have more extensive disease and should undergo more aggressive treatment modalities. Nevertheless, undetectable serum Tg should not be considered as a reliable criteria to exclude a minimal tumor burden in patients who have already been treated with (131)I.