Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7-gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy

Claudio Bellevicine, Ilaria Migliatico, Roberta Sgariglia, Mariantonia Nacchio, Elena Vigliar, Pasquale Pisapia, Antonino Iaccarino, Dario Bruzzese, Francesco Fonderico, Domenico Salvatore, Bernadette Biondi, Stefania Masone, Vincenzo Novizio, Francesco Scavuzzo, Domenico Serino, Maurizio De Palma, Maria Grazia Chiofalo, Gerardo Botti, Luciano Pezzullo, Vincenzo NuzzoStefano Spiezia, Giovanni De Chiara, Sergio Iorio, Giovanni Conzo, Giovanni Docimo, Antongiulio Faggiano, Massimo Bongiovanni, Umberto Malapelle, Annamaria Colao, Maria Triassi, Giancarlo Troncone

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis.

METHODS: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up.

RESULTS: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories.

CONCLUSIONS: The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalCancer cytopathology
Volume128
Issue number2
DOIs
Publication statusPublished - Feb 2020

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