title: Telomerase in differentiated thyroid cancer: promoter mutations, expression and localization.
abstract: Telomerase-reverse-transcriptase (TERT) promoter mutations have been recently described in tumors. In the present large series, TERT mutations were found in 12% of papillary thyroid cancers (PTCs) and in 14% of follicular thyroid cancers (FTCs), and were found to significantly correlate with older age at diagnosis and poorer outcome. Interestingly, the prognostic value of TERT mutations resulted to be significantly stronger than that of BRAF(V600E). Moreover, the outcome was not different among tumors with isolated TERT mutation and those with coexistent mutations (TERT/BRAF in PTCs or TERT/RAS in FTCs). TERT rs2853669 polymorphism was found in 44.4% of tumors. At WB, TERT was significantly more expressed in tumors than in normal samples, being the highest levels of expression recorded in TERT mutated cases. At IHC, in tumors and in metastatic lymph-nodes TERT staining was significantly higher in the cytoplasm than in the nucleus, whereas in normal tissue the degree of staining did not differ in the two cellular compartments. In conclusion, TERT mutations were shown to strongly correlate with a poorer outcome in differentiated thyroid tumors, and neither BRAF nor RAS mutation were found to confer an additional effect in the disease persistence. TERT protein was found to be more expressed in neoplastic than in normal tissues, and to display a different cellular localization, suggesting that it could contribute to thyroid cancer progression by mechanisms taking place in the cytoplasm.
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Muzza
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Division of Pathology, San Paolo Hospital, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Health Sciences, University of Milan, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Perrino
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: De Leo
authors.affiliation: Azienda USL of Modena, Italy; Department of Biomedicine, Metabolism and Neural Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Magnani
authors.affiliation: Azienda USL of Modena, Italy; Department of Biomedicine, Metabolism and Neural Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pignatti
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vigo
authors.affiliation: Azienda USL of Modena, Italy; Department of Biomedicine, Metabolism and Neural Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
authors.affiliation: Division of Pathology, San Paolo Hospital, Milan, Italy; Department of Health Sciences, University of Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bulfamante
authors.affiliation: Endocrine Surgery Unit, Fondazione IRCCS Ca'Granda, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vicentini
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Italy. Electronic address: laura.fugazzola@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
mesh_terms: D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000097:blood / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF; Epidemiology; Genomics; Outcome; RAS; TERT