OBJECTIVE Mutations in the RET proto-oncogene are found in about one third of sporadic medullary thyroid carcinomas (MTCs), mostly affecting codon 918. Glial cell line derived neurotropic factor (GDNF) and its membrane-bound GDNF family receptor alpha (GFRalpha-1), as well as neurturin (NTN) and its membrane-bound receptor GFRalpha-2 form a complex with the RET product, a receptor tyrosine kina...

• Approximately 10 to 25% of fine-needle aspiration (FNA) biopsies yield an indeterminate result often labeled as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN). The risk of malignancy typically varies between 15 and 30% for these categories. • Although many markers are in develo...

Thyroid cancer has a multifactorial aetiology resulting from the interaction of genetic and environmental factors. Several low penetrance susceptibility genes have been identified but their effects often vary between different populations. Somatic point mutations and translocations of the REarranged during Transfection (RET) proto-oncogene are frequently found in thyroid cancer. The aim of this...

The hyalinizing trabecular neoplasm (HTN) of the thyroid is an unusual and controversial lesion. Some consider it a peculiar type of papillary thyroid carcinoma (PTC) because of its nuclear features and presence of psammoma bodies. Others consider it an adenoma. Molecular studies have found RET/PTC translocations in some examples, supporting HTN as a PTC; however mutations in BRAF (another mark...

Oncogenic activation of the RET receptor tyrosine kinase is common in different human cancers. We found that the pyrazolo-pyrimidine PP1 inhibited RET-derived oncoproteins with a half maximal inhibitor concentration of 80 nM. Furthermore, RET/PTC3-transformed cells treated with 5 microM of PP1 lost proliferative autonomy and showed morphological reversion. PP1 prevented the growth of two human ...

In this issue of the JCEM, Walsh et al. (1) report the analytical validation of a molecular diagnostic method for indeterminate fine-needle aspiration (FNA) thyroid samples. Together with previous reports describing clinical performance and cost effectiveness of this method, this study highlights the capability of such a molecular test to reduce unnecessary surgery for benign thyroid diseases (...

Dedifferentiated thyroid cancer (DeTC) derived from follicular epithelium is often incurable because it does not respond to radioiodine, radiotherapy, or chemotherapy. In cases, RET/PTC rearrangements are found in 30%-40%, RAS mutations in about 10%, and BRAF mutations in around 40%-50%, with no overlap between these mutations results in papillary thyroid cancer, while a higher prevalence of BR...