BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas

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  • Marina N. Nikiforova
    Department of Pathology and Laboratory Medicine (M.N.N., M.G., P.W.B., Z.Z., Y.E.N.), Cincinnati, Ohio
  • Edna T. Kimura
    Division of Endocrinology (E.T.K., J.A.K., J.A.F.), University of Cincinnati, Cincinnati, Ohio
  • Manoj Gandhi
    Department of Pathology and Laboratory Medicine (M.N.N., M.G., P.W.B., Z.Z., Y.E.N.), Cincinnati, Ohio
  • Paul W. Biddinger
    Department of Pathology and Laboratory Medicine (M.N.N., M.G., P.W.B., Z.Z., Y.E.N.), Cincinnati, Ohio
  • Jeffrey A. Knauf
    Division of Endocrinology (E.T.K., J.A.K., J.A.F.), University of Cincinnati, Cincinnati, Ohio
  • Fulvio Basolo
    Dipartimento di Oncologia (F.B., R.G.), Pisa, Italy
  • Zhaowen Zhu
    Department of Pathology and Laboratory Medicine (M.N.N., M.G., P.W.B., Z.Z., Y.E.N.), Cincinnati, Ohio
  • Riccardo Giannini
    Dipartimento di Oncologia (F.B., R.G.), Pisa, Italy
  • Giuliana Salvatore
    Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.S., A.F., M.S.), University ‘Federico II’ c/o Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy
  • Alfredo Fusco
    Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.S., A.F., M.S.), University ‘Federico II’ c/o Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy
  • Massimo Santoro
    Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.S., A.F., M.S.), University ‘Federico II’ c/o Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy
  • James A. Fagin
    Division of Endocrinology (E.T.K., J.A.K., J.A.F.), University of Cincinnati, Cincinnati, Ohio
  • Yuri E. Nikiforov
    Department of Pathology and Laboratory Medicine (M.N.N., M.G., P.W.B., Z.Z., Y.E.N.), Cincinnati, Ohio

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<jats:title>Abstract</jats:title> <jats:p>Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hürthle cell, and medullary carcinomas, follicular and Hürthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T→A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.</jats:p>

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