title: CD8+ TIL recruitment may revert the association of MAGE A3 with aggressive features in thyroid tumors.
abstract: BACKGROUND
  We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker.
  
  
  METHODS
  We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8) were evaluated using immunohistochemistry and compared with clinical pathological features.
  
  
  RESULTS
  The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P < 0.0001), also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P = 0.0206) and in patients with stage II disease (P = 0.0107). MAGE A3+ tumors were more likely to present CD8+ TIL (P = 0.0346), and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease.
  
  
  CONCLUSIONS
  We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil.
authors.forename: Mariana Bonjiorno
authors.initials: MB
authors.lastname: Martins
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil.
authors.forename: Marjory Alana
authors.initials: MA
authors.lastname: Marcello
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil.
authors.forename: Fernando de Assis
authors.identifier: 0000-0001-5479-5329
authors.initials: Fde A
authors.lastname: Batista
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil.
authors.forename: Lucas Leite
authors.initials: LL
authors.lastname: Cunha
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil ; Department of Biological Sciences and Health, State University of Roraima (UERR), Rua Sete de Setembro 231, 69306-530 Boa Vista, RR, Brazil.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Morari
authors.affiliation: Department of Pathology, AC Camargo Hospital, Antonio Prudente Foundation, 211 Professor Antonio Prudente Street, 01509-010 São Paulo, SP, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Pathology, AC Camargo Hospital, Antonio Prudente Foundation, 211 Professor Antonio Prudente Street, 01509-010 São Paulo, SP, Brazil ; Laboratory of Investigative and Molecular Pathology, CIPED, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, 13083-887 Campinas, SP, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), 126 Tessália Vieira de Camargo Street, Barão Geraldo, 13083-887 Campinas, SP, Brazil.
authors.forename: Laura Sterian
authors.initials: LS
authors.lastname: Ward
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D063646:Carcinogenesis; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D016827:CD8 Antigens; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins
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