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Andres Elía Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Leo Saldain Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Silvia Lovisi Hospital de Agudos “Magdalena V de Martínez”, General Pacheco, Argentina

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Paula Martínez Vazquez Hospital de Agudos “Magdalena V de Martínez”, General Pacheco, Argentina

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Javier Burruchaga Hospital de Agudos “Magdalena V de Martínez”, General Pacheco, Argentina

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Caroline A Lamb Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Isabel Alicia Lüthy Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Federico Diez University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK

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Natalie Z M Homer University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK

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Ruth Andrew University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK

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Paola Rojas Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Claudia Lanari Instituto de Biología y Medicina Experimental (IBYME), CONICET, Argentina

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Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography–tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.

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Robin Schürfeld Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Leipzig, Germany

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Christina Pamporaki TU Dresden, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

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Mirko Peitzsch TU Dresden, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany

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Nada Rayes Center of Surgery, Division of Endocrine Surgery, Department for Visceral, Transplant, Thoracic, and Vascular Surgery, University of Leipzig, Leipzig, Germany

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Osama Sabri Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany

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Silvio Rohm Center of Surgery, Department for Visceral, Transplant, Thoracic, and Vascular Surgery, University of Leipzig, Leipzig, Germany
Center of Surgery, Department for Vascular Surgery, Diakonissen Hospital of Leipzig, Leipzig, Germany

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Ronald Biemann Institute of Clinical Chemistry and Laboratory Medicine, University of Leipzig, Leipzig, Germany

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Benjamin Sandner Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Leipzig, Germany

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Anke Tönjes Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Leipzig, Germany

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Graeme Eisenhofer TU Dresden, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

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Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin–norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

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Claire K Mulvey Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA

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Alan Paciorek Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

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Farhana Moon Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA

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Paige Steiding Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA

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Brandon Shih Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA

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Matthew A Gubens Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA

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Li Zhang Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

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Emily K Bergsland Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA

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Iona Cheng Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA

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Lung neuroendocrine tumors (NETs) have few known predictors of survival. We investigated associations of sociodemographic, clinicopathologic, and treatment factors with overall survival (OS) and lung cancer-specific survival (LCSS) for incident lung NET cases (typical or atypical histology) in the California Cancer Registry (CCR) from 1992 to 2019. OS was estimated with the Kaplan–Meier method and compared by sociodemographic and disease factors univariately with the log-rank test. We used sequential Cox proportional hazards regression for multivariable OS analysis. LCSS was estimated using Fine-Gray competing risks regression. There were 6038 lung NET diagnoses (5569 typical, 469 atypical carcinoid); most were women (70%) and non-Hispanic White (73%). In our multivariable model, sociodemographic factors were independently associated with OS, with better survival for women (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.57–0.68, P < 0.001), married (HR 0.76, 95% CI 0.70–0.84, P < 0.001), and residents of high socioeconomic status (SES) neighborhoods (HRQ5vsQ1 0.73, 95% CI 0.62–0.85, P < 0.001). Compared to cases with private insurance, OS was worse for cases with Medicare (HR 1.24, 95% CI 1.10–1.40, P < 0.001) or Medicaid/other public insurance (HR 1.45, 95% CI 1.24–1.68, P < 0.001). In our univariate model, non-Hispanic Black Californians had worse OS than other racial/ethnic groups, but differences attenuated after adjusting for stage at diagnosis. In our LCSS models, we found similar associations between sex and marital status on survival, but no differences in outcomes by SES or insurance. By race/ethnicity, American Indian cases had worse LCSS. In summary, beyond disease-related and treatment variables, sociodemographic factors were independently associated with survival in lung NETs.

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Chiara Alessandra Cella Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy

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Riccardo Cazzoli Department of Experimental Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Metal Targeted Therapy & Immunology lab, Childrens’ cancer institute, Sydney, NSW, Australia

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Nicola Fazio Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy

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Giuseppina De Petro Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy

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Germano Gaudenzi Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy

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Silvia Carra Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy

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Mauro Romanenghi Department of Experimental Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy

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Francesca Spada Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy

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Ilaria Grossi Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy

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Isabella Pallavicini Department of Experimental Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy

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Saverio Minucci Department of Experimental Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

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Giovanni Vitale Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.

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Paola De Marco Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy

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Enrica Romeo Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy

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Adele Vivacqua Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy

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Roberta Malaguarnera Endocrinology, Department of Health, University Magna Graecia of Catanzaro, Catanzaro, Italy

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Sergio Abonante Regional Hospital, Cosenza, Italy

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Francesco Romeo Regional Hospital, Cosenza, Italy

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Vincenzo Pezzi Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy

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Antonino Belfiore Endocrinology, Department of Health, University Magna Graecia of Catanzaro, Catanzaro, Italy

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Marcello Maggiolini Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy

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Walid Zeyghami Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Marie-Louise Uhre Hansen Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Kathrine Kronberg Jakobsen Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Christian Groenhøj Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Ulla Feldt-Rasmussen Department of Endocrinology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Clinical Sciences, University of Copenhagen, Copenhagen, Denmark

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Christian von Buchwald Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Clinical Sciences, University of Copenhagen, Copenhagen, Denmark

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Christoffer Holst Hahn Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Thyroid cancer (TC) represents the most common endocrine malignant tumor. Liquid biopsy has been suggested as a new and accurate biomarker in cancer. This systematic review analyzes the existing literature on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free DNA integrity index (cfDI), and their potential as biomarkers for TC, including the subtypes: differentiated (papillary and follicular), medullary, and anaplastic. A systematic search was performed in PubMed, Embase, and Cochrane databases for published articles in English between 1 January 1970 and 6 September 2022 (PROSPERO: CRD42022358592). The literature search generated a total of 635 articles. In total, 36 articles were included (patients = 2566). Four studies reported that higher levels of CTCs were associated with metastases and worse prognosis. Nineteen studies found the presence of mutated ctDNA in TC patients. The diagnostic accuracy in detecting BRAFV600E as ctDNA was determined in 11 studies regarding papillary TC. The pooled sensitivity, specificity, and diagnostic odds ratio were estimated at 56% (95% CI 36–74), 91% (95% CI 84–95) and 12 (95% CI 4.09–33.11), respectively. Four studies concluded that the cfDI was higher in patients with TC compared to benign thyroid lesions and healthy controls. The detection of CTCs, ctDNA, and cfDI may have a potential prognostic value in TC in relation to diagnosis, disease progression, and treatment efficacy. Despite the promising potential of CTCs, ctDNA, and cfDI in TC management, limitations hinder direct comparison and generalization of findings. Standardized methodologies, larger patient cohorts, and a consensus on relevant markers are needed to validate their clinical applicability and enhance TC management.

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Barbora Bulanova Pekova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Vlasta Sykorova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Karolina Mastnikova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Eliska Vaclavikova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Jitka Moravcova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Petr Vlcek Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Lucie Lancova Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Petr Lastuvka Departments of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Rami Katra Department of Ear, Nose and Throat, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Petr Bavor Department of Surgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Daniela Kodetova Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Martin Chovanec Department of Otorhinolaryngology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Jana Drozenova Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Radoslav Matej Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Jaromir Astl Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic

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Jiri Hlozek Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic

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Petr Hrabal Department of Pathology, Military University Hospital, Prague, Czech Republic

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Josef Vcelak Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Bela Bendlova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. ’True recurrences’ occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.

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Parvin Yenki The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Satyam Bhasin The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Liang Liu The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Noushin Nabavi The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Chi Wing Cheng The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Kevin J Tam The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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James W Peacock The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Hans H Adomat The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Tabitha Tombe The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Ladan Fazli The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Larissa Ivanova The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Christopher Dusek The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Shahram Khosravi The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Emma S Tomlinson Guns The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada

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Yuzhuo Wang The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Ralph Buttyan The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Martin E Gleave The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Christopher J Ong The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

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Intratumoral androgen biosynthesis contributes to castration-resistant prostate cancer progression in patients treated with androgen deprivation therapy. The molecular mechanisms by which castration-resistant prostate cancer acquires the capacity for androgen biosynthesis to bypass androgen deprivation therapy are not entirely known. Here, we show that semaphorin 3C, a secreted signaling protein that is highly expressed in castration-resistant prostate cancer, can promote steroidogenesis by altering the expression profile of key steroidogenic enzymes. Semaphorin 3C not only upregulates enzymes required for androgen synthesis from dehydroepiandrosterone or de novo from cholesterol but also simultaneously downregulates enzymes involved in the androgen inactivation pathway. These changes in gene expression correlate with increased production of androgens induced by semaphorin 3C in prostate cancer model cells. Moreover, semaphorin 3C upregulates androgen synthesis in LNCaP cell-derived xenograft tumors, likely contributing to the enhanced in vivo tumor growth rate post castration. Furthermore, semaphorin 3C activates sterol regulatory element-binding protein, a transcription factor that upregulates enzymes involved in the synthesis of cholesterol, a sole precursor for de novo steroidogenesis. The ability of semaphorin 3C to promote intratumoral androgen synthesis may be a key mechanism contributing to the reactivation of the androgen receptor pathway in castration-resistant prostate cancer, conferring continued growth under androgen deprivation therapy. These findings identify semaphorin 3C as a potential therapeutic target for suppressing intratumoral steroidogenesis.

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Roberto Olmos Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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José Miguel Domínguez Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Sergio Vargas-Salas Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Lorena Mosso Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Carlos E Fardella Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Gilberto González Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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René Baudrand Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Francisco Guarda Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Felipe Valenzuela Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Eugenio Arteaga Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Pablo Forenzano Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Flavia Nilo Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Nicole Lustig Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Alejandra Martínez Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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José M López Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile

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Francisco Cruz Department of Radiology, School of Medicine Pontificia Universidad Católica de Chile

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Soledad Loyola Department of Radiology, School of Medicine Pontificia Universidad Católica de Chile

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Augusto Leon Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Nicolás Droppelmann Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Pablo Montero Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Francisco Domínguez Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Mauricio Camus Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Antonieta Solar Department of Anatomic Pathology, School of Medicine Pontificia Universidad Católica de Chile

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Pablo Zoroquiain Department of Anatomic Pathology, School of Medicine Pontificia Universidad Católica de Chile

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Juan Carlos Roa Department of Anatomic Pathology, School of Medicine Pontificia Universidad Católica de Chile

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Estefanía Muñoz Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Elsa Bruce Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Rossio Gajardo Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Giovanna Miranda Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Francisco Riquelme Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Natalia Mena Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Hernán E González Department of Surgical Oncology, School of Medicine Pontificia Universidad Católica de Chile

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Molecular testing contributes to improving the diagnosis of indeterminate thyroid nodules (ITNs). ThyroidPrint® is a ten-gene classifier aimed to rule out malignancy in ITN. Post-validation studies are necessary to determine the real-world clinical benefit of ThyroidPrint® in patients with ITN. A single-center, prospective, noninterventional clinical utility study was performed, analyzing the impact of ThyroidPrint® in the physicians’ clinical decisions for ITN. Demographics, nodule characteristics, benign call rates (BCRs), and surgical outcomes were measured. Histopathological data were collected from surgical biopsies of resected nodules. Of 1272 fine-needle aspirations, 109 (8.6%) were Bethesda III and 135 (10.6%) were Bethesda IV. Molecular testing was performed in 155 of 244 ITN (63.5%), of which 104 were classified as benign (BCR of 67.1%). After a median follow-up of 15 months, 103 of 104 (99.0%) patients with a benign ThyroidPrint® remained under surveillance and one patient underwent surgery which was a follicular adenoma. Surgery was performed in all 51 patients with a suspicious for malignancy as per ThyroidPrint® result and in 56 patients who did not undergo testing, with a rate of malignancy of 70.6% and 32.1%, respectively. A higher BCR was observed in follicular lesion of undetermined significance (87%) compared to atypia of undetermined significance (58%) (P < 0.05). False-positive cases included four benign follicular nodules and six follicular and four oncocytic adenomas. Our results show that, physicians chose active surveillance instead of diagnostic surgery in all patients with a benign ThyroidPrint® result, reducing the need for diagnostic surgery in 67% of patients with preoperative diagnosis of ITN.

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