ABSTRACT
ABSTRACT: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that accounts for 5 to 10% of all thyroid cancers. A unique feature of MTC is the production of multiple tumor markers, such as calcitonin (CTN), carcinoembryonic antigen, and chromogranin A. The typical diagnosis is represented by a solitary nodule, often associated with nodal metastases, and elevated basal or stimulated CTN levels. However, even this infrequent malignancy has a variable phenotype. The majority of MTCs are sporadic, but about 20% result from a germline mutation in the proto-oncogene RET. Dominant-activating or gain-of-function mutations in RET lead to the constitutive activation of receptor tyrosine kinases and downstream pathways involved in cell survival and proliferation. These mutations are related to an autosomal dominant cancer syndrome that can manifest either as a single disorder (familial MTC (fMTC)) or as multiple endocrine neoplasia (MEN) syndrome-type 2A or 2B. Despite the rarity of these syndromes, early diagnosis is very important since MTC is a potentially lethal disease if not promptly treated. In this context, genetic evaluation can swiftly diagnose fMTC and MEN and, furthermore, can identify at-risk subjects who require prophylactic surgery. Thanks to the introduction of RET genetic screening in the workup of all patients with MTC (both hereditary and apparently sporadic types), the number and type of recognized RET mutations have grown over the last 10 years. Even though MTC is an infrequent human cancer, it has long been considered a model for the study of molecular abnormalities that underlie the initiation and
4.1 Introduction ............................................................................................................................40 4.2 Parafollicular Cells and CTN .................................................................................................40 4.3 Genetics of C-Cell Disease .....................................................................................................44
