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Analysis of BRAF Point Mutation and RET/PTC Rearrangement Refines the Fine-Needle Aspiration Diagnosis of Papillary Thyroid Carcinoma

Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche and Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.S., M.S.), and Dipartimento di Scienze Biomorfologiche e Funzionali (A.C., I.M., G.T., L.P.), University ‘Federico II,’ 80131 Napoli, Italy; Dipartimento di Oncologia (R.G., P.F., F.B.), University of Pisa, 56126 Pisa, Italy; and Department of Pathology and Laboratory Medicine and Division of Endocrinology (J.A.F., Y.E.N.), University of Cincinnati, Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Massimo Santoro, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, University ‘Federico II’ via. Sergio Pansini 5, 80131 Naples, Italy. E-mail: masantor{at}unina.it.

Point mutations in BRAF are genetic hallmarks of papillary thyroid carcinoma (PTC). In this retrospective study, we examined thyroid aspirates and corresponding paraffin-embedded surgical samples for the presence of BRAF mutations. Altogether, we examined 96 cases, including 69 PTCs, 19 follicular adenomas, and eight nontoxic nodular goiters for BRAF; 60 of these samples were also examined for RET/PTC rearrangements. The results were correlated with the cytological diagnosis and the final histopathology. The BRAF mutation (V599E) was detected in 38% of the samples that were PTC on histopathology; RET/PTC was found in 18% of the PTC cases. In all the cases, the presence of the genetic alteration was confirmed in the surgically resected tumor. The identification of BRAF mutation and RET/PTC refined the diagnosis of PTC in five of 15 samples that were considered either indeterminate or insufficient at cytology. No mutation was found in aspirates of follicular adenomas and nontoxic nodular goiters. These results indicate that BRAF mutation and RET/PTC rearrangements are molecular markers of PTC that can be applied to FNA in adjunct to traditional cytology.

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