Molecular genetics of thyroid tumors and surgical decision-making

The study of thyroid tumor genetics has great relevance to surgeons and fac ilitates understanding tumor pathogenesis, prediction of tumor behavior, an d management decisions. The genes implicated can be broadly categorized as oncogenes or tumor-suppressor genes. The RET oncogene has well established roles in the development of both papillary (PTC) and medullary (MTC) thyroi d carcinoma. Genetic screening for germline RET mutations in members of mul tiple endocrine neoplasia type II (MEN-II) families is now widely performed , and prophylactic thyroidectomy in gene carriers is advisable at an early age. Patients with apparently sporadic MTC can also be screened to rule out familial disease. The demonstration of a RET rearrangement in a patient's PTC may have prognostic significance, but as yet there are no management im plications. The thyrotropin receptor (TSH-R) and Gs alpha become oncogenic through point mutation and are associated with the development of toxic thy roid adenomas. The ras oncogene is implicated in the early stages of develo pment of several thyroid tumor types. Tumor-suppressor genes also have a ro le in thyroid tumor formation. The p53 gene appears to be involved in the p rocess of transformation to the anaplastic phenotype and the PTEN gene in t he development of follicular adenomas but not carcinomas, There is still li mited evidence for the so called adenoma-carcinoma sequence of the thyroid follicular cell. Loss of heterozygosity studies have enabled identification of tumor-suppressor genes, and their findings suggests differences in the pathogenesis of PTCs compared with follicular cancers, Surgical derision ma king will benefit from these basic molecular advances, which rapidly transl ates into improved patient management.