Expression of iodine metabolism genes in children and adolescents with thyroid cancer

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 459-496-Thyroid Neoplasia & Case Reports
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-471
Maria Isabel Cunha Vieira Cordioli*1, Lais de Sousa Moraes2, Paloma Besson2, Maria Tereza Seixas Alves2, Rosana Delcelo2, Osmar Monte3, Carlos Alberto Longui4, Adriano Namo Cury5 and Janete Maria Cerutti6
1Federal University of São Paulo, Sao Paulo, Brazil, 2Federal University of São Paulo, 3Santa Casa de São Paulo, Sao Paulo, Brazil, 4Santa Casa De Sao Paulo, Sao Paulo, Brazil, 5Santa Casa de Sao Paulo, Sao Paulo-SP, Brazil, 6Federal University of Sao Paulo, Sao Paulo, Brazil
Background: Differentiated thyroid cancer (DTC) is a rare pathology in childhood and accounts for 0.5-1.5% of all tumors in this age(1). Previous studies reported marked differences in clinical presentation of this tumor in children and adolescents, with a higher incidence of cervical and distant metastasis and recurrence rates comparing to adult population(2,3).  Despite these clinical features, the DTC has characteristically a greater responsiveness to radioiodine treatment and a better prognosis in childhood (4,5). Differences in expression of iodine metabolism genes according to age could explain this disparity in clinical and treatment response. Although it has been demonstrated that the expression of iodine metabolism genes is lower in adult DTC, mainly in BRAF V600E-positive tumors, little is know about their expression in pediatric group (6). Objectives: To investigate the association of histological and clinical parameters with iodine metabolism genes expression and BRAF V600E mutational status in pediatric DTC. Methods: A total of 49 patients (34 DTC and 15 benign lesions) under 18 years of age submitted to thyroid surgery were investigated. Results: The occurrence of BRAF V600E mutation was detected in 6 (17,64%) patients. The expression of thyroglobulin (TG) was lower in malignant tumors (p=0.0112), specially in patients with BRAF V600E mutation (p=0.0062), and it was associated to an increase in cervical metastasis rates (p=0.0095). The expression of sodium-iodide symporter (NIS), pendred syndrome gene (PDS/SCL26A4),  thyroperoxidase (TPO) and TSH receptor (TSH-R) did not show a significant difference between benign and malignant tumors. Conclusions: The clinical features of DTC are markedly different in pediatric population, what may be associated with different molecular profile in this group. Different from what has been reported in adult population, a lower expression of TG associated with normal expression of other iodine metabolism gene was observed in this study. This find is compatible with recent studies that reported the role of the TG as a potent negative feedback regulator of follicular function (7). This difference in iodine metabolism genes expression between pediatrics and adult patients may explain some of the discrepancies verified in clinical features, evolution and treatment response according to age. The better understanding of the mechanisms involved in pediatric DTC may be useful for future developments of therapeutic approaches toward this group of patients.

(1) Hogan AR, Zhuge Y, Perez EA, et al,. Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res. 2009;156:167-72 (2) Leboulleux S, Baudin E, Hartl DW,et al,.Follicular cell-derived thyroid cancer in children. Horm Res. 2005;63:145-51. (3) Neiva F, Mesquita J, Paco Lima S, et al., Thyroid carcinoma in children and adolescents: a retrospective review. Endocrinol Nutr. 2012;59:105-8.(4) Chow SM, Law SC, Mendenhall WM, et al,. Differentiated thyroid carcinoma in childhood and adolescence-clinical course and role of radioiodine. Pediatr Blood Cancer. 2004;42:176-83. (5) Hod N, Hagag P, Baumer M, et al,. Differentiated thyroid carcinoma in children and young adults: evaluation of response to treatment. Clin Nucl Med. 2005;30:387-90. (6) Espadinha C, Santos JR, Sobrinho LG, et al,. Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency. Clin Endocrinol (Oxf). 2009;70:629-35. (7) Suzuki K, Kawashima A, Yoshihara A, Akama T, Sue M, Yoshida A, Kimura HJ. Role of thyroglobulin on negative feedback autoregulation of thyroid follicular function and growth. J Endocrinol. 2011;209:169-74.

Nothing to Disclose: MICVC, LDSM, PB, MTSA, RD, OM, CAL, ANC, JMC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: FAPESP - São Paulo Research Foundation