AUTHOR=Romei Cristina , Elisei Rossella 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2012.00054

DOI=10.3389/fendo.2012.00054

ISSN=1664-2392

ABSTRACT=<p>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 (<italic>RET</italic>) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first <italic>RET</italic> rearrangement, named <italic>RET</italic>/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the <italic>RET</italic> 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 <italic>RET</italic>/PTC rearrangements have been reported but the two most common are <italic>RET</italic>/PTC1 and <italic>RET</italic>/PTC3. Ionizing radiations are responsible for the generation of <italic>RET</italic>/PTC rearrangements, as supported by <italic>in vitro</italic> studies and by the evidence that <italic>RET</italic>/PTC, and particularly <italic>RET</italic>/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar <italic>RET</italic> rearrangements. The overall prevalence of <italic>RET</italic>/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 <italic>RET</italic>/PTC rearrangements and the PTC prognosis. <italic>RET</italic>/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, <italic>RET</italic>/PTC1 rearrangement does not correlate with any clinical–pathological characteristics of PTC. Moreover, the <italic>RET</italic> protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between <italic>RET</italic>/PTC rearrangements and the expression level of the thyroid differentiation genes was observed. Recently, a diagnostic role of <italic>RET</italic>/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.</p>