title: pmTOR is a marker of aggressiveness in papillary thyroid carcinomas.
abstract: Activation of the mTOR pathway has been observed in thyroid cancer, but the biologic consequences regarding tumor behavior and patient prognosis remain poorly explored.
  
  
  
  We aimed to evaluate the associations of the mTOR pathway with clinicopathologic and molecular features and prognosis through the immunocharacterization of pmTOR and pS6 expression (as readouts of the pathway) in a series of 191 papillary thyroid carcinomas.
  
  
  
  pmTOR expression was associated with distant metastases (P = .05) and persistence of disease (P = .05). Cases with greater expression of pmTOR were submitted to more131I treatments (r[102] = 0.2; P = .02) and a greater cumulative dose of radioactive iodine (r[100] = 0.3; P = .01). Positive pmTOR expression showed to be an independent risk factor for distant metastases (odds ratio = 18.2; 95% confidence interval 2.1-157.9; P = .01). In contrast, pS6 expression was associated with absence of extrathyroid extension (P = .001), well-defined tumor margins (P = .05), and wild-type BRAF status (P = .01). There was no correlation between the expression of pmTOR and pS6 expression (r[140] = 0.1; P = .3).
  
  
  
  pmTOR expression is an indicator of aggressive, metastatic papillary thyroid carcinoma, being possibly implicated in refractoriness to therapy, while pS6 expression is associated with less aggressive pathologic features. Further studies are needed to understand better the biologic consequences of activation of the mTOR pathway in the behavior of thyroid cancer, namely the contribution of other pmTOR downstream effectors.
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors: Catarina
authors: C
authors: Tavares
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar of the University of Porto (ICBAS), Porto, Portugal.
authors: Maria João
authors: MJ
authors: Coelho
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Department of Endocrinology, Diabetes, and Metabolism, University and Hospital Center of Coimbra, Coimbra, Portugal; Medical Faculty, University of Coimbra, Coimbra, Portugal.
authors: Miguel
authors: M
authors: Melo
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; University and Hospital Center of Coimbra, Coimbra, Portugal.
authors: Adriana Gaspar
authors: AG
authors: da Rocha
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors: Ana
authors: A
authors: Pestana
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors: Rui
authors: R
authors: Batista
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal.
authors: Catarina
authors: C
authors: Salgado
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal.
authors: Catarina
authors: C
authors: Eloy
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors: Luciana
authors: L
authors: Ferreira
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal; Department of Pathology, Hospital de S.João, Porto, Portugal.
authors: Elisabete
authors: E
authors: Rios
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal; Department of Pathology, Hospital de S.João, Porto, Portugal.
authors: Manuel
authors: M
authors: Sobrinho-Simões
authors: Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal; Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal. Electronic address: psoares@ipatimup.pt.
authors: Paula
authors: P
authors: Soares
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002291:Carcinoma, Papillary; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D027981:Symporters / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000099209:Sodium-Iodide Symporters
chemical_list: D015415:Biomarkers; D027981:Symporters; D058570:TOR Serine-Threonine Kinases; D000099209:Sodium-Iodide Symporters; C546842:MTOR protein, human