BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy

Angela Santoro, Giuseppe Pannone, Maria Antonia Carosi, Arianna Francesconi, Edoardo Pescarmona, Giuseppe Maria Russo, Antonia Feola, Simona Losito, Renato Franco, Luigi Nappi, Gabriella Aquino, Gaetano De Rosa, Marina Di Domenico, Pantaleo Bufo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1174-1182
Number of pages9
JournalJournal of Cellular Biochemistry
Volume114
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • BRAF
  • immunohistochemistry
  • promoter methylation
  • RASSF1A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Santoro, A., Pannone, G., Carosi, M. A., Francesconi, A., Pescarmona, E., Russo, G. M., Feola, A., Losito, S., Franco, R., Nappi, L., Aquino, G., De Rosa, G., Di Domenico, M., & Bufo, P. (2013). BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy. Journal of Cellular Biochemistry, 114(5), 1174-1182. https://doi.org/10.1002/jcb.24460