Biological Characteristics of Thyroid Carcinomas

ABSTRACT

Thyroid carcinomas show a broad spectrum of neoplastic phenotypes with distinct molecular events. In a thyroid multistep tumorigenesis model for differentiated thyroid carcinomas of follicular cell origin(DTCs), normal thyrocytes are transformed to differentiated thyroid cancer and progress to poorly differentiated thyroid carcinomas(PDTCs) and ultimately anaplastic thyroid carcinomas(ATCs), through the progressive accumulation of alterations in genes related with cell proliferation and differentiation. PDTCs and ATCs lose expression of thyroid-specific genes such as thyroglobulin, TSH-R, sodium/iodide symporter(NIS) genes and thyroid specific transcription factors. These tumors unfortunately may grow rapidly, invade adjacent structures and spread to other parts of the body. Biological characteristics of thyroid carcinomas are also quite different according to histological types. Most of DTCs show favorable biological behavior and keep their differentiated functions such as iodine uptake and TSH responsiveness. Unlike the other human carcinomas, presence of regional lymph node metastasis does not alter outcome significantly but age at diagnosis profoundly affect biological behavior of DTCs. Many cases of ATCs appear to be associated with preexisting DTC and p53 mutation plays an important role in this terminal dedifferentiation. ATC is highly aggressive and lethal. Medullary thyroid carcinomas(MTCs) originate from calcitonin secreting C cell by point mutation of ret protooncogene. Some specific ret mutations(genotypes) predict the phenotypic expression of hereditary MTC, guiding the timing of thyroidectomy. Understanding of biological characteristics and behavior of thyroid carcinomas help us to make a logical decision for optimal timing and extent of surgical treatment and postoperative adjuvant therapy.