Molecular Biology of Thyroid Cancer

Thyroid is a H-shaped gland localised in front of trachea at the base of the neck, whose main functions are the synthesis, the storage and the secretion of thyroid hormones under the control of the hypothalamic–pituitary axis. Thyroid is comprised of spherical follicles filled with colloid that are lined by cuboidal/flat epithelial cells denoted follicular cells (or thyrocytes). The other hormone-producing cells in the thyroid gland are scattered within follicles, and are denoted para-follicular cells (or C cells). Whereas follicular cells are responsible for iodine uptake and thyroid hormone synthesis, C cells are dedicated to the production of calcitonin (Dumont et al., 1992). Cancers that arise in the thyroid gland represent the most common malignancy of the endocrine system and accounts for approximately 1% of all newly diagnosed cancer cases in Western countries, with estimates of annual incidence rates of 12 cases per 100,000 in North America and 5.6 new cases per 100,000 in Europe (Gilliland et al., 2009). Incidence rates of thyroid cancer widely vary worldwide, possibly because of inherent ethnic geographical or environmental differences that include iodine deficiency and radiation exposure. For instance the incidence of thyroid cancer is high in the Chinese and Filipino population of Hawaii (119 cases/million women and 45 cases/million men, respectively) and it is relatively low in Poland (14 cases/million women and 4 cases/million men, respectively) (Ain, 1995). The most common forms of thyroid carcinoma derive either from thyroid follicular epithelial cells or from C cells (Sherman, 2003). The former include welldifferentiated carcinoma (WDTC) divided into (PTC) and follicular thyroid carcinoma (FTC) -, poorly differentiated carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) (Rosai et al., 1992; DeLellis et al., 2004). PTC is the most frequent type of thyroid malignancy, and accounts for approximately 80-85% of all cases, FTC accounts for approximately 10-15% of all thyroid tumors whereas PDTC and ATC are rare aggressive malignancies (2% of all thyroid cancer) that can develop either directly or from pre-existing well-differentiated PTC and FTC. Thyroid cancer derived from para-follicular C cells is denoted Medullary Thyroid Carcinoma (MTC). MTC is a relatively rare malignancy (<5%) and will not be discussed here. Most neoplasms derived from thyroid follicular epithelial cells are indolent tumours that can be effectively treated by surgical resection and/or radioactive-iodine administration. Usually, PTC and FTC are well-differentiated tumours with a fairly good prognosis that are generally curable with current treatments (Sherman,