Active Surveillance in RET Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of RET gene. Subjects harboring a germline RET mutation without any clinical signs of MTC are defined as gene carriers (...

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Autores principales:	Alessandro Prete, Antonio Matrone, Carla Gambale, Valeria Bottici, Virginia Cappagli, Cristina Romei, Liborio Torregrossa, Laura Valerio, Elisa Minaldi, Maria Cristina Campopiano, Loredana Lorusso, Laura Agate, Eleonora Molinaro, David Viola, Teresa Ramone, Chiara Mulè, Raffaele Ciampi, Fulvio Basolo, Rossella Elisei
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	medullary thyroid cancer calcitonin MEN2 gene carriers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fef97fe63a684afea5b6ee3bac515ccf
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spelling	oai:doaj.org-article:fef97fe63a684afea5b6ee3bac515ccf2021-11-11T15:34:51ZActive Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia10.3390/cancers132155542072-6694https://doaj.org/article/fef97fe63a684afea5b6ee3bac515ccf2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5554https://doaj.org/toc/2072-6694Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of <i>RET</i> gene. Subjects harboring a germline <i>RET</i> mutation without any clinical signs of MTC are defined as gene carriers (GCs), for whom guidelines propose a prophylactic thyroid surgery. We evaluate if active surveillance of GCs, pursuing early thyroid surgery, can be safely proposed and if it allows safely delaying thyroid surgery in children until adolescence/adulthood. We prospectively followed 189 GCs with moderate or high risk germline <i>RET</i> mutation. Surgery was planned in case of: elevated basal calcitonin (bCT) and/or stimulated CT (sCT); surgery preference of subjects (or parents, if subject less than 18 years old); other reasons for thyroid surgery. Accordingly, at <i>RET</i> screening, we sub-grouped GCs in subjects who promptly were submitted to thyroid surgery (Group A, <i>n</i> = 67) and who were not (Group B, <i>n</i> = 122). Group B was further sub-grouped in subjects who were submitted to surgery during their active surveillance (Group B1, <i>n</i> = 22) and who are still in follow-up (Group B2, <i>n</i> = 100). Group A subjects presented significantly more advanced age, bCT and sCT compared to Group B. Mutation <i>RET</i><sup>V804M</sup> was the most common variant in both groups but it was significantly less frequent in Group A than B. Analyzing age, bCT, sCT and genetic landscape, Group B1 subjects differed from Group B2 only for sCT at last evaluation. Group A subjects presented more frequently MTC foci than Group B1. Moreover, Group A MTCs presented more aggressive features (size, T and N) than Group B1. Accordingly, at the end of follow-up, all Group B1 subjects presented clinical remission, while 6 and 12 Group A MTC patients had structural and biochemical persistent disease, respectively. Thank to active surveillance, only 13/63 subjects younger than 18 years at <i>RET</i> screening have been operated on during childhood and/or adolescence. In Group B1, three patients, while actively surveilled, had the possibility to reach the age of 18 (or older) and two patients the age of 15, before being submitted to thyroid surgery. In Group B2, 12 patients become older than 18 years and 17 older than 15 years. In conclusion, we demonstrated that an active surveillance pursuing an early thyroid surgery could be safely recommended in GCs. This patient-centered approach permits postponing thyroid surgery in children until their adolescence/adulthood. At the same time, we confirmed that genetic screening allows finding hidden MTC cases that otherwise would be diagnosed much later.Alessandro PreteAntonio MatroneCarla GambaleValeria BotticiVirginia CappagliCristina RomeiLiborio TorregrossaLaura ValerioElisa MinaldiMaria Cristina CampopianoLoredana LorussoLaura AgateEleonora MolinaroDavid ViolaTeresa RamoneChiara MulèRaffaele CiampiFulvio BasoloRossella EliseiMDPI AGarticlemedullary thyroid cancercalcitoninMEN2gene carriersNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5554, p 5554 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	medullary thyroid cancer calcitonin MEN2 gene carriers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	medullary thyroid cancer calcitonin MEN2 gene carriers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Alessandro Prete Antonio Matrone Carla Gambale Valeria Bottici Virginia Cappagli Cristina Romei Liborio Torregrossa Laura Valerio Elisa Minaldi Maria Cristina Campopiano Loredana Lorusso Laura Agate Eleonora Molinaro David Viola Teresa Ramone Chiara Mulè Raffaele Ciampi Fulvio Basolo Rossella Elisei Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
description	Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of <i>RET</i> gene. Subjects harboring a germline <i>RET</i> mutation without any clinical signs of MTC are defined as gene carriers (GCs), for whom guidelines propose a prophylactic thyroid surgery. We evaluate if active surveillance of GCs, pursuing early thyroid surgery, can be safely proposed and if it allows safely delaying thyroid surgery in children until adolescence/adulthood. We prospectively followed 189 GCs with moderate or high risk germline <i>RET</i> mutation. Surgery was planned in case of: elevated basal calcitonin (bCT) and/or stimulated CT (sCT); surgery preference of subjects (or parents, if subject less than 18 years old); other reasons for thyroid surgery. Accordingly, at <i>RET</i> screening, we sub-grouped GCs in subjects who promptly were submitted to thyroid surgery (Group A, <i>n</i> = 67) and who were not (Group B, <i>n</i> = 122). Group B was further sub-grouped in subjects who were submitted to surgery during their active surveillance (Group B1, <i>n</i> = 22) and who are still in follow-up (Group B2, <i>n</i> = 100). Group A subjects presented significantly more advanced age, bCT and sCT compared to Group B. Mutation <i>RET</i><sup>V804M</sup> was the most common variant in both groups but it was significantly less frequent in Group A than B. Analyzing age, bCT, sCT and genetic landscape, Group B1 subjects differed from Group B2 only for sCT at last evaluation. Group A subjects presented more frequently MTC foci than Group B1. Moreover, Group A MTCs presented more aggressive features (size, T and N) than Group B1. Accordingly, at the end of follow-up, all Group B1 subjects presented clinical remission, while 6 and 12 Group A MTC patients had structural and biochemical persistent disease, respectively. Thank to active surveillance, only 13/63 subjects younger than 18 years at <i>RET</i> screening have been operated on during childhood and/or adolescence. In Group B1, three patients, while actively surveilled, had the possibility to reach the age of 18 (or older) and two patients the age of 15, before being submitted to thyroid surgery. In Group B2, 12 patients become older than 18 years and 17 older than 15 years. In conclusion, we demonstrated that an active surveillance pursuing an early thyroid surgery could be safely recommended in GCs. This patient-centered approach permits postponing thyroid surgery in children until their adolescence/adulthood. At the same time, we confirmed that genetic screening allows finding hidden MTC cases that otherwise would be diagnosed much later.
format	article
author	Alessandro Prete Antonio Matrone Carla Gambale Valeria Bottici Virginia Cappagli Cristina Romei Liborio Torregrossa Laura Valerio Elisa Minaldi Maria Cristina Campopiano Loredana Lorusso Laura Agate Eleonora Molinaro David Viola Teresa Ramone Chiara Mulè Raffaele Ciampi Fulvio Basolo Rossella Elisei
author_facet	Alessandro Prete Antonio Matrone Carla Gambale Valeria Bottici Virginia Cappagli Cristina Romei Liborio Torregrossa Laura Valerio Elisa Minaldi Maria Cristina Campopiano Loredana Lorusso Laura Agate Eleonora Molinaro David Viola Teresa Ramone Chiara Mulè Raffaele Ciampi Fulvio Basolo Rossella Elisei
author_sort	Alessandro Prete
title	Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
title_short	Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
title_full	Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
title_fullStr	Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
title_full_unstemmed	Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia
title_sort	active surveillance in <i>ret</i> gene carriers belonging to families with multiple endocrine neoplasia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fef97fe63a684afea5b6ee3bac515ccf
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Active Surveillance in <i>RET</i> Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia

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