Medullary thyroid carcinoma and some of its particularities

Abstract

Various studies of medullary thyroid carcinoma have found its apoptosis rate to be very low. Tumor growth is usually progressive but in some cases, rapid progression and high proliferation are seen. Some mutations of the RET proto-oncogene are thought to have a direct or indirect effect on this clinical process. Five characteristics are significantly associated with poor survival: tumor necrosis, squamous histology, age older than 45 years, oxyphilic tumor cells together with a lack of intermediary cytoplasm cells, and finally, less than 50% of tumor cells immunoreactive to calcitonin. Although recent studies have identified the gene involved in this cancer, its molecular pathogenesis has not yet been elucidated. Medullary thyroid carcinoma is rare, but practitioners must be familiar with it because it presents specific therapeutic and diagnostic problems. Sensitive and specific direct genetic diagnosis of the principal mutation of the RET proto-oncongene is possible in patients with familial thyroid carcinoma or multiple endocrine neoplasia type 2. Screening is based on the immunoradiometric assay of calcitonin levels before and after pentagastrin stimulation in different populations: healthy subjects, persons with family members who have medullary thyroid carcinoma, patients with thyroid nodules or autoimmune chronic thyroiditis. Recently a somatic mutation on RET codon 918 was reported in patients with medullary thyroid carcinoma and those with C cell hyperplasia and multiple endocrine neoplasia together. This finding suggests that this particular mutation may play a role in tumorigenesis. Compared with patients with endocrine neoplasia syndromes type 2A and 2B, these patients appeared to have a syndrome clinically overlapping these, and its genetic basis may be distinct from them. Family members of patients with medullary thyroid carcinoma must be screened for this inherited disease. The mutations associated with medullary thyroid carcinoma and parathyroid tumors together appear to be closely related to the centromeric region of chromosome 10. At three months of age, Wag/Rij rats show hypersecretion under secretagogues and C cell hyperplasia; both signs are described as "pretumoral" in humans. A battery of markers are useful even though the gene for multiple endocrine neoplasia type 2 gene has recently been thought to be located in the pericentromeric region of chromosome 10 in white Europeans.