Calcitonin estimation in patients with nodular goiter and its significance for early detection of MTC: european comments to the guidelines of the American Thyroid Association

One of the most discussed and controversial issue in the management of thyroid nodules is the need to perform a routine measurement of serum Calcitonin (Ct) in all cases. The American Thyroid Association guidelines do not recommend in favor or against this procedure since they retain that there are not enough evidences that it can determine an advantage to the health outcomes of these patients. This is not the view of many European experts who met in Lisbon in 2009 at the European Thyroid Association-Cancer Research Network meeting to discuss all the still open controversial issues on the management of medullary thyroid cancer patients.This paper is focused on the routine measurement of serum Ct in all patients with thyroid nodule(s): the evidences, the rational and the benefits of this procedure are deeply analysed following the discussion that was done in Lisbon. The conclusions reached at that time are reported in detail

RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma

Thyroid carcinoma is the most frequent endocrine cancer accounting for 5–10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the expression level of the thyroid differentiation genes was observed. Recently, a diagnostic role of RET/PTC rearrangements has been proposed. It can be searched for in the mRNA extracted from cytological sample especially in case with indeterminate cytology. However, both the fact that it can be present in a not negligible percentage of benign cases and the technical challenge in extracting mRNA from cytological material makes this procedure not applicable at routine level, at least for the moment

Ruolo delle tecniche di sequenziamento di ultima generazione nella gestione del paziente con carcinoma tiroideo

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Qualità della vita nei pazienti con microcarcinoma papillare della tiroide in funzione del trattamento: tiroidectomia totale con o senza terapia radiometabolica ablativa

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I tempi della tiroidectomia nella MEN2

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Classificatore genetico predittivo della benignità di noduli tiroidei a citologia indeterminata

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Diagnosi per immagini istologiche, immunoistochimiche e sonografiche di un raro caso di plasmocitoma scarsamente differenziato della tiroide

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DICER1 somatic mutations strongly impair miRNA processing even in benign thyroid lesions

The alteration of miRNA processing is a driver event in several tumors including thyroid cancer. In particular, somatic DICER1 mutations, reported in follicular-patterned lesions, are shared by benign as well as malignant tumors. In the present study, we investigated the effects of alterations in the miRNA processing genes on the miRNA profile. The study included 19 follicular adenomas (FAs) and 22 follicular variant of papillary thyroid carcinomas (FVPTCs). The mutational status in the hot spot regions of DICER1, DROSHA, TARBP2, DGCR8 and the most commonly affected genes in thyroid tumors was investigated on both tumor and paired normal tissues. The miRNA profile and the mRNA expression levels of DICER1, DROSHA, TARBP2, DGCR8 and XPO5 were also evaluated. Two DICER1 RNase IIIb domain mutations were found in FAs. These lesions presented a considerable loss of 5p miRNAs. Fifteen miRNAs were specifically deregulated in DICER1-mutant lesions compared to FAs and FVPTCs. These miRNAs regulate crucial pathways in cancer such as Hippo, p53 and TGF-beta signalling. DICER1 somatic mutations in the RNase IIIb domain are not specific for malignancy, but the miRNA imbalance that they cause is remarkable, especially with regard to the loss of 5p miRNAs. DICER1-mutant lesions have a characteristic miRNA deregulation, which is different from that of FVPTCs; nevertheless, this impairment is consistent with malignant transformation. Further studies providing the real risk of malignancy associated with DICER1 mutations and the evolution of DICER1-mutant lesions are needed to make them useful in the clinical practice