Endocrine Abstracts

Objectives: Distant metastases in MTC adversely affect disease prognosis. Somatic mutations in spMTC as well as Variant Allele Frequency (VAF) have been related to tumor burden, disease course and the response to TKIs. The aim of this study is to report three cases of nucleotide (nt) insertions/deletions (indels) in the RET oncogene in relation to disease course/response to TKIs.Methods: Of 195 spMTC patients followed-up in Dept. Clinical Therap...

Background: Human cancer is characterized by the accumulation of somatic alterations including base substitutions, indels, structural rearrangements and somatic copy number alteration (CNA), either gain or loss, of chromosomes that can be responsible either for initiation and/or cancer progression. About 80% of Sporadic Medullary Thyroid Carcinoma (sMTC) harbor RET or RAS somatic alterations with a negative prognostic role for the presence of the RET mutation; a few s...

Housekeeping genes (HK) are commonly used as controls for the normalization of the RNA amount in quantitative RT-PCR experiments. The question whether their expression is influenced by the metabolic state of the patient and/or the tumour transformation is still unresolved and until now, HK genes have been used in quantitative studies without considering that their expression could be different in tumor with respect to normal tissue. Aim of this study was to identify HK genes e...

Background: One of the major limits of gene therapy with sodium iodide symporter (NIS), which enables cells to be subjected to radioiodine therapy, is that NIS transfected cells rapidly release the intracellular iodine.Materials and methods: We transfected two human anaplastic (FRO) and medullary (TT) thyroid cancer derived cell lines, unable to take up iodine, with human NIS cDNA. The possibility of increasing the iodine retention time by treating cells...

We previously found that two cell lines (ARO and FRO) derived from anaplastic thyroid cancer and one (TT) deriving from medullary thyroid cancer did not respond to the retinoic acid (RA) treatment. We supposed that it was related to the lack of the RA receptor RAR beta mRNA expression. It has been suggested that the promoter methylation was one possible cause of loss of RAR beta expression.We analyzed the methylation status of RAR beta promoter in ARO, F...

Background: Genotype-phenotype correlations between various RET mutations and clinical manifestations of MEN 2 syndrome are well established. A discussion is still open if the FMTC phenotype really exists or if it is just a MEN2A variant. Aim of this study was to verify if the phenotype corresponding to the V804M germline mutation is restricted to FMTC.Methods: During the last 25 years, we have identified 200 families with a hereditary form of M...

Genetic intratumor heterogeneity has been recently demonstrated in some solid human cancers and a few years ago RET mutated and not mutated cells were described in medullary thyroid carcinoma (MTC). Nobody reported the presence of two different RET mutations.Aim of our study was to investigate the RET somatic mutation profile in primary MTC (pMTC) and in the corresponding metastatic tissues (mets).We studied pMTC and mets of 22 MTC...

18FDG-PET is based on the capability of tumor cells to take up glucose. An increment in expression of the glucose transporter 1 (GLUT1) has been observed in thyroid tumors with poor prognosis but very few data are available about the expression of other glucose transporters in thyroid. Here, we study the expression and function of GLUT isoforms 1, 2, 3, 4, 6, 8, 10, 12 in human thyroid carcinoma cell lines ARO and FRO (anaplastic carcinoma), NPA (poorly-differentiated papillar...

In a previous study we demonstrated that retinoic acid (RA) decreased the growth only of thyroid carcinoma cell lines expressing RA receptor β (RAR β) and that decitabine (5-Aza-CdR) re-induced RARβ expression. The aim of this study was to analyze the effects induced by the combined treatment with RA and 5-Aza-CdR in the same thyroid cancer cell lines.We studied the effect of 5-Aza-CdR 800 nM and RA 1 μM on the expression of thyroid s...

Mutations in the RET proto-oncogene are responsible for multiple endocrine neoplasia type II. Somatic RET mutations were described in 50% of medullary thyroid carcinoma (MTC). We describe here a novel germline mutation of the RET gene detected in an apparentely sporadic MTC.The index case was a 67 years old patient who arrived at our observation for a bilateral laterocervical linfoadenopathy. The patient was clinically evaluated for thyroid function and ...