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Somatostatin (SST) is a 28-amino-acid cyclic neuropeptide mainly secreted by neurons and endocrine cells. A major interest for SST receptors (SSTR) as target for in vivo diagnostic and therapeutic purposes was born since a series of stable synthetic SST-analouges PET became available, being the native somatostatin non feasible for clinical use due to the very low metabolic stability. The rationale for the employment of SST-analogues to image cancer is both based on the expression of SSTR by tumor and on the high affinity of these compounds for SSTR. The primary indication of SST-analogues imaging is for neuroendocrine tumors (NETs), which usually express a high density of SSTR, so they can be effectively targeted and visualized with radiolabeled SST-analogues in vivo. Particularly, SST-analogues imaging has been widely employed in gastroenteropancreatic (GEP) NETs. Nevertheless, a variety of tumors other than NETs expresses SSTR thus SST-analogues imaging can also be used in these tumors, particularly if treatment with radiolabeled therapeutic SST-analouges PET is being considered. The aim of this paper is to provide a concise overview of the role of positron emission tomography/computed tomography (PET/CT) with 68Ga-radiolabeled SST-analouges PET in tumors other than GEP-NETs.

// Greta Gandolfi 1 , Moira Ragazzi 2 , Dario de Biase 3 , Michela Visani 4 , Eleonora Zanetti 2 , Federica Torricelli 1 , Valentina Sancisi 1 , Mila Gugnoni 1 , Gloria Manzotti 1 , Luca Braglia 5 , Silvio Cavuto 5 , Domenico Franco Merlo 5 , Giovanni Tallini 4 , Andrea Frasoldati 6 , Simonetta Piana 2 and Alessia Ciarrocchi 1 1 Laboratory of Translational Research, Azienda Unita Sanitaria Locale di Reggio Emilia - IRCCS, Reggio Emilia 42123, Italy 2 Pathology Unit, Department of Oncology, Azienda Unita Sanitaria Locale di Reggio Emilia - IRCCS, Reggio Emilia 42123, Italy 3 Department of Pharmacology and Biotechnology (FaBiT), University of Bologna, 40139 Bologna, Italy 4 Department of Medicine, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale-DIMES, Anatomic Pathology Unit, Bellaria Hospital, University of Bologna, 40139 Bologna, Italy 5 Research and Statistics Unit, Azienda Unita Sanitaria Locale di Reggio Emilia-IRCCS, Reggio Emilia, 42123, Italy 6 Endocrinology Unit, Azienda Azienda Unitaria Sanitaria Locale di Reggio Emilia , Reggio Emilia 42123, Italy Correspondence to: Alessia Ciarrocchi, email: Alessia.Ciarrocchi@ausl.re.it Keywords: papillary thyroid carcinomas; distant metastases; copy number alterations; next generation sequencing; TERT duplication Received: September 14, 2017 Accepted: October 27, 2017 Published: December 01, 2017 ABSTRACT Background: Papillary Thyroid Carcinomas (PTCs) are generally indolent tumors. However, a small but significant percentage of PTCs behaves aggressively, progressing to a diffuse metastatic spreading and leading to patient’s death. The lack of reliable markers for predicting the metastatic behavior of these tumors prevents a correct risk based stratification of the disease, thus contributing to the issue of patients’ overtreatment. In this study we aimed at identifying genetic features associated with the development of distant metastasis in PTCs. Results: We showed that DM PTCs are characterized by a moderate degree of copy number alterations but display low level of microsatellite instability and a low mutational burden. We identified duplication of Chr1q, duplication of Chr5p harboring the TERT genomic locus and mutations of TERT promoter as distinctive features of DM PTCs. These three genetic variables defined a signature (THYT1) that was significantly associated with a metastatic behavior and a shortened survival. We analyzed the THYT1 signature in PTCs fine needle aspirate biopsies (FNAB) and we demonstrating the applicability of this signature as a molecular marker in the pre-operative diagnostic setting of PTCs. Materials and Methods: A consecutive series of 2,937 thyroid malignancies, diagnosed at the Arcispedale S. Maria Nuova - IRCCS, Italy between 1978 and 2015 were searched to retrieve those who developed distant metastasis (DM, n = 50). We performed a deep profiling to explore the genomic landscape of these tumors. Conclusions: Overall our data identify the first genetic signature that independently predicts metastasis and negative outcome of PTCs, and lay the basis for the possible application of the THYT1 as prognostic marker to improve risk-based stratification and management of PTC patients.

BACKGROUND: Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential association with unfavorable clinical features in a large cohort of mPTCs. METHODS: A total of 431 mPTCs cases were collected from six Italian institutions, and TERT promoter mutational status was assessed by a next-generation sequencing approach. RESULTS: TERT promoter mutations were found in 4.7% of the analyzed mPTCs, showing that even microcarcinomas carry mutations in this gene. Correlation analysis showed that TERT promoter mutations are not associated with aggressive features or clinical outcome in the cohort analyzed. CONCLUSIONS: TERT mutations are present but uncommon in mPTCs. Apparently, in mPTCs, the occurrence of TERT mutations is not correlated with unfavorable clinical features