title: Gene expression of thyroid-specific transcription factors may help diagnose thyroid lesions but are not determinants of tumor progression.
abstract: OBJECTIVE
  The role of thyroid-specific transcription factors in thyroid malignancy is still poorly understood, so we investigate thyroid-specific transcription factors gene expression both in benign and in malignant thyroid nodules, aiming to study a possible clinical utility of these molecules.
  
  
  METHODS
  We quantified TTF-1, FOXE1 and PAX8 mRNA levels, relating their expression to diagnostic and prognostic features of thyroid tumors. RNA was extracted from 4 normal thyroid tissues, 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesion tissues [49 goiter and 50 follicular adenomas (FA)].
  
  
  RESULTS
  Levels of mRNA of both FOXE1 (P < 0.0001) and PAX8 (P < 0.0001) genes, but not TTF-1 (P = 0.7056), were higher in benign than in malignant thyroid lesions. FOXE1 was able to identify malignant nodules with 75.8 % sensitivity, 76.1 % specificity, 75.8 % positive predictive value, 76.1 % negative predictive value and 75.9 % accuracy. PAX8 was able to identify malignancy with 60.6 % sensitivity, 81.1 % specificity, 76.9 % positive predictive value, 66.4 % negative predictive value and 70.6 % accuracy. Both FOXE1 and PAX8 gene expression patterns were also able to differentiate FA from the follicular variant of PTC-FVPTC. However, the investigated gene expression was neither associated with any clinical feature of tumor aggressiveness nor associated with recurrence or survival.
  
  
  CONCLUSIONS
  We suggest that FOXE1 and PAX8 gene expression patterns may help to diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions, but are not determinants of thyroid tumor progression.
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil. fernando815@gmail.com.
authors.forename: F A
authors.initials: FA
authors.lastname: Batista
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Ward
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Marcello
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: M B
authors.initials: MB
authors.lastname: Martins
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: K C
authors.initials: KC
authors.lastname: Peres
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Torricelli
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: N E
authors.initials: NE
authors.lastname: Bufalo
authors.affiliation: Department of Pathology, AC Camargo Hospital - Antonio Prudente Foundation, Rua Professor Antônio Prudente, 211, Liberdade, São Paulo, São Paulo, 01509-010, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Molecular Biology and Genetic Engineering Center (CBMEG), University of Campinas (Unicamp), Avenida Cândido Rondon, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-875, Brazil.
authors.forename: M J
authors.initials: MJ
authors.lastname: da Silva
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), School of Medical Sciences, University of Campinas (Unicamp), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: L V M
authors.initials: LV
authors.lastname: Assumpção
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000072636:PAX8 Transcription Factor / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics; D014157:Transcription Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D012333:RNA, Messenger; C504003:TTF1 protein, human; D014157:Transcription Factors
keywords: Diagnostic; FOXE1; Follicular thyroid lesion; PAX8; TTF-1; Thyroid nodules