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.

Bellevicine C1, Migliatico I1, Sgariglia R1, Nacchio M1, Vigliar E1, Pisapia P1, Iaccarino A1, Bruzzese D1, Fonderico F2, Salvatore D1, Biondi B2, Masone S2, Novizio V3, Scavuzzo F3, Serino D3, De Palma M4, Chiofalo MG5, Botti G6, Pezzullo L5, Nuzzo V7, Spiezia S8, De Chiara G9, Iorio S10, Conzo G11, Docimo G10, Faggiano A12, Bongiovanni M13, Malapelle U1, Colao A2, Triassi M1, Troncone G1; Tiroide Network.

Author information

1: Department of Public Health, University of Naples Federico II, Naples, Italy.
2: Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
3: Department of Endocrinology, Aziena Ospedaliera di Rilievo Nazionale A. Cardarelli, Naples, Italy.
4: Department of Surgery, Aziena Ospedaliera di Rilievo Nazionale A. Cardarelli, Naples, Italy.
5: Thyroid and Parathyroid Surgery Unit, IRCCS G. Pascale, Naples, Italy.
6: IRCCS G. Pascale, Naples, Italy.
7: Department of Endocrinology, Hospital of the Sea-Azienda Sanitaria Locale Naples 1 Center, Naples, Italy.
8: Department of Endocrine Surgery, Hospital of the Sea-Azienda Sanitaria Locale Naples 1 Center, Naples, Italy.
9: Department of Pathology, Aziena Ospedaliera di Rilievo Nazionale San Giuseppe Moscati, Avellino, Italy.
10: Department of Medical, Surgical, Neurological, Metabolic, and Aging Sciences, University of Campania Luigi Vanvitelli, Caserta, Italy.
11: Department of Cardiothoracic and Respiratory Sciences, University of Campania Luigi Vanvitelli, Caserta, Italy.
12: Department of Experimental Medicine, University of Rome Sapienza, Rome, Italy.
13: Cytopathology, Synlab SA, Lausanne, Switzerland.

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.