Follicular Histotypes of Oncocytic Thyroid Carcinomas Do Not Carry Mutations of the BRAF Hot‐spot

Abstract

The BRAF V600E mutation is the most prevalent genetic aberration in papillary thyroid carcinomas (PTCs), and it is found exclusively in RET/PTC-negative tumors. In oncocytic (Hürthle cell, oxyphilic) thyroid tumors, the presence of RET/PTC rearrangements is associated with either the conventional papillary histotype or the "solid" Hürthle cell tumors, whereas all predominantly follicular oncocytic carcinomas do not harbor RET/PTC chimeras. Although 12% of tumors of the follicular variant of PTC carry BRAF mutations, none of the few oncocytic follicular thyroid adenomas (oncoAd) or carcinomas (oncoFTC) published worldwide tested positive. An aspired molecular-based classification of oncocytic thyroid tumors is in need of additional evidence on BRAF mutations in the follicular histotype. A series of 44 oncocytic thyroid tumors with well-documented clinicopathological data was subjected to BRAF mutation analysis (complete exon 15) by automated sequencing. The series of oncocytic thyroid tumors consisted of 21 adenomas (oncoAds: 17 females, 4 males; mean age, 54.5 years; range, 27-80 years), 20 follicular carcinomas (oncoFTCs: 14 females, 6 males; mean age, 61.4 years; range, 39-80 years), and 3 "classic" papillary carcinomas (oncoPTCs: 3 females; mean age, 58.1 years; range, 46-70 years; 3x T2 tumors). The follicular variants of oncocytic cancers are divided into 11x T2, 5x T3, and 4x T4 tumor stages (International Union Against Cancer [UICC] TNM 5th edition). None of the 44 neoplasms of the presented series demonstrated genetic alterations in the BRAF hot-spot region (exon 15, codons 599-601). Congruently, 0/10 oncoAd and 0/20 oncoFTC described in the literature so far carried BRAF V600E mutations. Our results add to the evidence that, in contrast to follicular variants of oncoPTCs, predominantly follicular oncocytic thyroid tumors harbor neither RET/PTC rearrangements nor BRAF mutations. Furthermore, the findings support the concept that oncocytic neoplasms of the thyroid gland are oncocytic counterparts of the respective histotype (adenoma, FTC, PTC, or poorly differentiated thyroid carcinoma) rather than a separate tumor entity. Molecular characterization of oncocytic thyroid malignancies for RET/PTC or BRAF genetic alterations may help with (preoperative) classification and prognostic evaluation of these tumors.