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The preeminence of growth pattern and invasiveness and the limited influence of BRAF and RAS mutations in the occurrence of papillary thyroid carcinoma lymph node metastases

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Abstract

Prognostic factors indicative of papillary thyroid carcinoma (PTC) aggressive behaviour remain incompletely established partially due to the different composition of the series on record regarding the relative proportion of classic PTC (CPTC) and follicular variant PTC (FVPTC) subtypes. Several clinico-morphological features of PTC, together with the occurrence of BRAF mutations, are still not fully accepted as markers of aggressiveness. In the present clinico-pathological study of a series of 75 CPTC and FVPTC cases, we evaluated the relative contribution of the morphological features of the tumours and their BRAF and N-RAS status for the occurrence of nodal metastases. The morphological features most closely related to the occurrence of nodal metastases were extra-thyroid extension and poorly circumscribed growth pattern, in both CPTC and FVPTC. Additional features significantly associated to nodal metastases were multicentricity in the CPTC and vascular invasion in the FVPTC group. BRAF V600E mutation was detected in 29% of tumours, 41% of CPTC and 16% of FVPTC; N-RAS Q61R mutation was detected in 6% of tumours, 3% of CPTC and 10% of FVPTC. BRAF mutation was significantly more frequent in the CPTC group and in females, and it was detected only in patients older than 20 years, suggesting a late tumourigenic effect in the development of PTC. BRAF mutation was not significantly associated to any of the other studied features related to aggressiveness or nodal metastases. These results highlight the importance of infiltrative growth pattern and invasiveness over the presence of BRAF mutation in classic and follicular variant PTC for the development of nodal metastases.

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Acknowledgements

This work was partially supported by the grant Prof. Edward Limbert SPEND/GENZYME–Year 2007. Part of the data reported in this study were obtained in the project “Identificação de factores prognósticos e de selecção terapêutica em carcinomas diferenciados da tireoide”, which is supported by Fundação Calouste Gulbenkian. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partly supported by the Fundação para a Ciência e Tecnologia.

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Authors and Affiliations

  1. Pathology Department, Hospital de São João, Oporto, Portugal

    Catarina Eloy & Manuel Sobrinho-Simões

  2. Pathology Department, Medical Faculty, University of Porto, Oporto, Portugal

    Catarina Eloy, Paula Soares & Manuel Sobrinho-Simões

  3. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Oporto, Portugal

    Catarina Eloy, Joana Santos, Paula Soares & Manuel Sobrinho-Simões

  4. Dentistry Faculty, University of Porto, Oporto, Portugal

    Catarina Eloy

  5. Anatomic Pathology, Hospital de São João, Alameda Professor Hernani Monteiro, 4200-451, Oporto, Portugal

    Catarina Eloy

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  1. Catarina Eloy
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Eloy, C., Santos, J., Soares, P. et al. The preeminence of growth pattern and invasiveness and the limited influence of BRAF and RAS mutations in the occurrence of papillary thyroid carcinoma lymph node metastases. Virchows Arch 459, 265–276 (2011). https://doi.org/10.1007/s00428-011-1133-7

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