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BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas

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Abstract

Somatic mutations of the BRAF gene (BRAFV599E and BRAFK600E) were found to be closely associated with different histotypes of papillary thyroid carcinoma (PTC). The V599E mutation is highly prevalent in PTC with a papillary or mixed papillary follicular growth pattern, and the K600E mutation is apparently restricted to the follicular variant of PTC. It is usually accepted that thyroid malignancies may follow a progression path from well-differentiated to poorly differentiated (PDC) and undifferentiated (UC) carcinomas. One would expect that at least some of the less differentiated carcinomas would harbour the genetic alterations of pre-existing well-differentiated tumours. In order to find the prevalence of BRAF mutations in PDC and UC, we screened a series of 19 PDCs and 17 UCs, as well as 3 UC-derived cell lines, for both mutation types. The group of PDCs was restricted to the so-called insular and insular-like PDCs, thus excluding PTCs with solid, insular or trabecular foci of growth and PDCs displaying typical PTC nuclei. No BRAF mutations were detected in any of the 19 cases of PDC, whereas 6 of the UCs (35%) and one UC-derived cell line presented the BRAFV599E mutation. The BRAFK600E mutation was not detected in any case. We conclude that UC may progress from BRAFV599E-mutated PTC. The absence of BRAF mutations in our series of PDC supports the assumption that pure insular and insular-like PDCs are more closely related to follicular carcinoma than to PTC.

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Acknowledgements

This study was supported by Fundação para a Ciência e Tecnologia POCTI/FEDER (POCTI/NSE/48171/2002). We are grateful to FCT for grant support to Vítor Trovisco (FSRH/BD/13055/2003) and Ana Sofia Rocha (FSRH/BD/21775/99). We would also like to thank Prof. J.E. Dumont and Prof. Marc Mareel for providing the cell lines included in this study.

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Authors and Affiliations

  1. IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), R. Roberto Frias s/n, 4200, Porto, Portugal

    Paula Soares, Vítor Trovisco, Ana Sofia Rocha, Tália Feijão, Ana Paula Rebocho & Manuel Sobrinho-Simões

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

    Paula Soares & Manuel Sobrinho-Simões

  3. Department of Pathology, Hospital São João, Porto, Portugal

    Elsa Fonseca & Manuel Sobrinho-Simões

  4. Department of Pathology, Medical Faculty, University of São Paulo, Brazil

    Inês Vieira de Castro

  5. Department of Pathology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain

    José Cameselle-Teijeiro

  6. Department of Surgery B, Hospital São João, Porto, Portugal

    Manuel Cardoso-Oliveira

Authors
  1. Paula Soares
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  2. Vítor Trovisco
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  3. Ana Sofia Rocha
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  4. Tália Feijão
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  5. Ana Paula Rebocho
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  6. Elsa Fonseca
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  7. Inês Vieira de Castro
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  8. José Cameselle-Teijeiro
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  9. Manuel Cardoso-Oliveira
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  10. Manuel Sobrinho-Simões
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Corresponding author

Correspondence to Manuel Sobrinho-Simões.

Additional information

Paula Soares and Vítor Trovisco contributed equally to this work.

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Soares, P., Trovisco, V., Rocha, A.S. et al. BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Arch 444, 572–576 (2004). https://doi.org/10.1007/s00428-004-1018-0

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  • DOI: https://doi.org/10.1007/s00428-004-1018-0

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