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Multicenter Study
. 2020 Feb;128(2):107-118.
doi: 10.1002/cncy.22217. Epub 2019 Dec 10.

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  1 , Ilaria Migliatico  1 , Roberta Sgariglia  1 , Mariantonia Nacchio  1 , Elena Vigliar  1 , Pasquale Pisapia  1 , Antonino Iaccarino  1 , Dario Bruzzese  1 , Francesco Fonderico  2 , Domenico Salvatore  1 , Bernadette Biondi  2 , Stefania Masone  2 , Vincenzo Novizio  3 , Francesco Scavuzzo  3 , Domenico Serino  3 , Maurizio De Palma  4 , Maria Grazia Chiofalo  5 , Gerardo Botti  6 , Luciano Pezzullo  5 , Vincenzo Nuzzo  7 , Stefano Spiezia  8 , Giovanni De Chiara  9 , Sergio Iorio  10 , Giovanni Conzo  11 , Giovanni Docimo  10 , Antongiulio Faggiano  12 , Massimo Bongiovanni  13 , Umberto Malapelle  1 , Annamaria Colao  2 , Maria Triassi  1 , Giancarlo Troncone  1 ; Tiroide Network
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Free article
Multicenter Study

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 et al. Cancer Cytopathol. 2020 Feb.
Free article

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.

Keywords: 7-gene test; cancer; cytopathology; fine-needle aspiration; molecular diagnostics; thyroid.

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References

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