pmTOR is a marker of aggressiveness in papillary thyroid carcinomas

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pmTOR is a marker of aggressiveness in papillary thyroid carcinomas

Monday, 26.09.2016

Catarina Tavares1,2,3, Maria João Coelho1,2,4, Miguel Melo1,2,5,6, Adriana Gaspar da Rocha1,2,7, Ana Pestana1,2,3, Rui Batista1,2,3, Catarina Salgado1,2, Catarina Eloy1,2, Luciana Ferreira1,2,3, Elisabete Rios3,8,9, Manuel Sobrinho-Simões1,2,3,8,9 and Paula Soares1,2,3,8

1-Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto;

2-Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP);

3-Faculdade de Medicina da Universidade do Porto;

4-Instituto de Ciências Biomédicas Abel Salazar (ICBAS);

5-Departamento de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar e Universitário de Coimbra;

6-Faculdade de Medicina da Universidade de Coimbra;

7-Centro Hospitalar e Universitário de Coimbra;

8-Departamento de Patologia e Oncologia, Faculdade de Medicina da Universidade do Porto;

9- Departamento de Patologia, Hospital de S. João.

Background: Activation of them TOR pathway has been observed in thyroid cancer, but the biologic consequences regarding tumor behavior and patient prognosis remain poorly explored. Methods: We aimed to evaluate the associations of the mTOR pathway with clinicopathologic and molecular features and prognosis through the immuno-characterization of pmTOR and pS6 expression (as readouts of the pathway) in a series of 191 papillary thyroid carcinomas. Results: pmTOR expression was associated with distant metastases (P=0.05) and persistence of disease (P=0.05). Cases with greater expression of pmTOR were submitted to more 131I treatments (r(102)=0.2; P=0.02) and a greater cumulative dose of radioactive iodine (r(100)=0.3; P=0.01). Positive pmTOR expression showed to be an independent risk factor for distant metastases (OR=18.2; 95% confidence interval 2.1-157.9; P=0.01). In contrast, pS6 expression was associated with absence of extrathyroidal extension (P=0.001), well-defined tumor margins (P=0.05), and wild type BRAF status (P=0.01). There was no correlation between the expression of pmTOR and pS6 expression (r(140)=0.1; P=0.3). Conclusions: 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 in order 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.

Journal: Surgery