Molecular Pathogenesis of Tumors of Thyroid Follicular Cells

Abstract

This chapter will consider current information on the pathogenesis of tumors of follicular thyroid cells. The genetic events associated with medullary thyroid cancers will be described separately, as they are derived from a different cell type and have distinct characteristics (please see Chapter 4). In 1997, an estimated 16,100 patients were diagnosed with thyroid cancer in the U.S. Of the two major forms of differentiated cancer derived from thyroid follicular cells, papillary carcinomas are by far the most common. By contrast, follicular thyroid carcinomas are now quite rare (1). Iodide intake is a key environmental factor determining the relative incidence of follicular and papillary cancers. The association of follicular carcinomas with iodine deficiency suggests that this type of tumor often develops within glands subjected to a chronic proliferative drive. Many of them probably arise from pre-existing adenomas, and as such fit the paradigm of clonal evolution through a multistep process involving progressive transformation through somatic mutations of genes important in growth control. By contrast, papillary carcinomas do not have a readily identifiable benign precursor lesion. Although most cases of papillary carcinoma arise in patients with no known risk factor, a history of prior exposure to radiation as a child increases the relative risk for this disease, as discussed in Chapters 1 and 2.