BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy

Authors

  • Angela Santoro,

    1. Department of Clinical and Experimental Medicine, Section of Anatomic Pathology, University of Foggia, Foggia, Italy
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  • Giuseppe Pannone,

    1. Department of Clinical and Experimental Medicine, Section of Anatomic Pathology, University of Foggia, Foggia, Italy
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  • Maria Antonia Carosi,

    1. Division of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy
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  • Arianna Francesconi,

    1. Division of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy
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  • Edoardo Pescarmona,

    1. Division of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy
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  • Giuseppe Maria Russo,

    1. Department of Otorhinolaryngology, University of Foggia, Foggia, Italy
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  • Antonia Feola,

    1. Department of Biochemistry, Biophysics and General Pathology, Second Univesity of Naples, Naples, Italy
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  • Simona Losito,

    1. Section of Pathological Anatomy, Fourth Section of Maxillofacial Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ‘G.Pascale’, Naples, Italy
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  • Renato Franco,

    1. Section of Pathological Anatomy, Fourth Section of Maxillofacial Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ‘G.Pascale’, Naples, Italy
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  • Luigi Nappi,

    1. Department of Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy
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  • Gabriella Aquino,

    1. Section of Pathological Anatomy, Fourth Section of Maxillofacial Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ‘G.Pascale’, Naples, Italy
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  • Gaetano De Rosa,

    1. Department of Biomorphological and Functional Sciences, Pathological Section, University of Naples, Italy
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  • Marina Di Domenico,

    Corresponding author
    1. Department of Biochemistry, Biophysics and General Pathology, Second Univesity of Naples, Naples, Italy
    2. Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, Pennsylvania
    • Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
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  • Pantaleo Bufo

    1. Department of Clinical and Experimental Medicine, Section of Anatomic Pathology and Cytopathology, University of Foggia, Foggia, Italy and IRCCS CROB—Centro di Riferimento Oncologico di Basilicata, Rionero in Vulture, Potenza, Italy
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  • Disclosure Statement: No competing financial interests exist.

  • Angela Santoro and Giuseppe Pannone contributed equally to this study.

Abstract

Aim of this work is to provide a detailed comparison of clinical-pathologic features between well-differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status. We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT-PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB-HRP technique. An overall higher degree of RASSF1A over-expression than normal thyroid parenchyma surrounding tumors (P < 0.05) has been found in all malignant well-differentiated lesions. Moreover, statistically significant higher levels of RASSF1A expression were observed in differentiated cancers associated to an inflammatory autoimmune background (P = 0.01). Amplifiable DNA for LC PCR with LightMix® kit BRAF V600E was obtained in nine PTCs, four FVPTCs, five ATCs, and one control. The V600E mutation was found in 13 of 18 (72%) tumors. BRAF was mutated in 6 of 9 (66%) classical PTC, in 2 of 4 (50%) follicular variant PTC and in all ACs (100%). The overall frequency of RASSF1A promoter methylation observed was 20.5% (9 cases out 44). Hypermethylation of RASSF1A in primary tumors was variable according to histotypes ranging from100% (5/5) in ACs to only 12.5% (4/32) in PTCs. We show a correlation between RASSF1A methylation status and RASSF1A protein expression. Finally, we conclude that BRAF V600E mutation and RASSF1A methylation were pathogenetic event restricted to a subgroup of PTC/FVPTCs in early stage and to clinically aggressive ATCs. J. Cell. Biochem. 114: 1174–1182, 2013. © 2012 Wiley Periodicals, Inc.

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