title: Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression.
abstract: OBJECTIVE
  Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical-biological features.
  
  
  METHODS
  Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart.
  
  
  RESULTS
  THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression.
  
  
  CONCLUSIONS
  Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis.
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rosignolo
authors.affiliation: Department of Health Sciences, University of Catanzaro 'Magna Graecia', 88100, Catanzaro, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Maggisano
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sponziello
authors.affiliation: Department of Health Sciences, University of Catanzaro 'Magna Graecia', 88100, Catanzaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Celano
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, University of Rome "Sapienza", 00161, Rome, Italy.
authors.forename: C R T
authors.initials: CR
authors.lastname: Di Gioia
authors.affiliation: Department of Health Sciences, University of Catanzaro 'Magna Graecia', 88100, Catanzaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Agostino
authors.affiliation: Department of Surgical Sciences, University of Rome "Sapienza", 00161, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Giacomelli
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Verrienti
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dima
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Pecce
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Rome "Sapienza", Viale del Policlinico155, 00161, Rome, Italy. cosimo.durante@uniroma1.it.
authors.forename: C
authors.initials: C
authors.lastname: Durante
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002291:Carcinoma, Papillary; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Papillary thyroid carcinoma; Thyroid hormone receptor; miRNA