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Thyroid cancer is the most common type of endocrine malignancy with an incidence that has steadily increased over the past three decades. Epithelial malignant cancers of the thyroid arise from two different types of parenchymal cells, follicular and parafollicular. Follicular cells are predominately involved in the production of thyroid hormones. The parafollicular cells are responsible for the production of calcitonin.
Well-differentiated thyroid carcinomas (DTC) account for 90% of all thyroid cancers, while medullary thyroid carcinomas (MTC) account for 5-9%, and anaplastic carcinomas for the remaining 1-2%. Well-differentiated carcinomas are further subdivided histologically as papillary thyroid cancer (80–85%), follicular thyroid cancer (10–15%) and Hurtle cell carcinoma (3–5%). Overall, DTCs have a very good prognosis with long-term disease-free survival close to 95% for papillary thyroid cancers (PTC) and 80% for follicular thyroid cancers (FTC). Their treatment is based on a three-pronged approach that includes thyroidectomy, radioactive iodine therapy and hormonal suppression (TSH) with thyroid replacement hormone. Their most important prognostic factor is distant metastasis which is found in only 5% of patients but carry a high mortality rate at 1 year (50%). In general, DTCs do not respond to chemotherapy (Espinosa, Porchia, and Ringel 2007; Sippos and Mazzaferri 2008).
Medullary thyroid cancers are clinically classified as sporadic or familial cancers. Sporadic MTCs occur as localized cancers with infrequent lymph node involvement (unifocal) and correspond to 70% of all cases, while familial cancers are typically diagnosed as advanced disease (multifocal) in the remaining 30% of the cases. Familial MTCs have been described as part of the MEN 2a syndrome which includes the presence of pheochromocytoma and parathyroid hyperplasias, and of the MEN 2b syndromes that also include pheochromocytoma and mucosal neuromas and/or gastrointestinal ganglioneuromas. These cancers have a 5-year survival of 80 to 90%, and for a few decades, surgery was the only effective therapy (Nosé 2011). Just recently, the tyrosine kinase inhibitor, vandetanib, was approved by the FDA for treatment of metastatic MTC. It is the only targeted agent FDA approved for any thyroid cancer (Deshpande et al. 2011).
Thyroid cancers harbor multiple gene mutations or rearrangements which are mutually exclusive. Affected genes include RET, BRAF, PI3KCA, and RAS (Kimura et al. 2003).
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