Volume 82, Issue 6 pp. 892-899
Original Article

Twenty years of lesson learning: how does the RET genetic screening test impact the clinical management of medullary thyroid cancer?

Cristina Romei

Corresponding Author

Cristina Romei

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Correspondence: Cristina Romei, Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. Tel.: +39050544723; Fax: +39050578772; E-mail: [email protected]Search for more papers by this author
Alessia Tacito

Alessia Tacito

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Eleonora Molinaro

Eleonora Molinaro

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Laura Agate

Laura Agate

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Valeria Bottici

Valeria Bottici

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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David Viola

David Viola

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Antonio Matrone

Antonio Matrone

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Agnese Biagini

Agnese Biagini

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Francesca Casella

Francesca Casella

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Raffaele Ciampi

Raffaele Ciampi

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Gabriele Materazzi

Gabriele Materazzi

Department of Surgical Medical Molecular Pathology, University of Pisa, Pisa, Italy

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Paolo Miccoli

Paolo Miccoli

Department of Surgical Medical Molecular Pathology, University of Pisa, Pisa, Italy

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Liborio Torregrossa

Liborio Torregrossa

Department of Surgical Medical Molecular Pathology, University of Pisa, Pisa, Italy

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Clara Ugolini

Clara Ugolini

Department of Surgical Medical Molecular Pathology, University of Pisa, Pisa, Italy

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Fulvio Basolo

Fulvio Basolo

Department of Surgical Medical Molecular Pathology, University of Pisa, Pisa, Italy

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Paolo Vitti

Paolo Vitti

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Rossella Elisei

Rossella Elisei

Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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First published: 02 December 2014
Citations: 44

Summary

Objective

Medullary thyroid carcinoma (MTC) is a rare disease that can be inherited or sporadic; its pathogenesis is related to activating mutations in the RET gene.

Design

This study describes our 20-year experience regarding RET genetic screening in MTC.

Patients and methods

We performed RET genetic screening in 1556 subjects, 1007 with an apparently sporadic MTC, 95 with a familial form and 454 relatives of RET-positive patients with MTC.

Results

A germline RET mutation was found in 68 of 1007 (6·7%) patients with sporadic MTC, while 939 patients with MTC were negative for germline RET mutations. We then identified a total of 137 gene carriers (GC). These subjects initiated a clinical evaluation for the diagnosis of MEN 2. A total of 139 MEN 2 families have been followed: 94 FMTC, 33 MEN 2A and 12 MEN 2B. Thirty-three different germline RET mutations were identified. Codon 804 was the most frequently altered codon particularly in FMTC (32/94, 34%), while codon 634 was the most frequently altered codon in MEN 2A (31/33, 94%); MEN 2B cases were exclusively associated with an M918T mutation at exon 16.

Conclusions

Our 20-year study demonstrated that RET genetic screening is highly specific and sensitive, and it allows the reclassification as hereditary of apparently sporadic cases and the identification of GC who require an adequate follow-up. We confirmed that FMTC is the most prevalent MEN 2 syndrome and that it is strongly correlated with noncysteine RET mutations. According to these findings, a new paradigm of follow-up of hereditary MTC cases might be considered in the next future.

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