• thyroid
• mRNA
• NIFTP
• expression

BACKGROUND: Follicular-patterned nodules are a hard diagnostic challenge. They includes both benign (follicular adenoma, FA) and malignant (follicular thyroid carcinoma, FTC and follicular variant of papillary thyroid carcinoma, FVPTC) lesions, however their differential diagnosis can be often achieved only after diagnostic surgery and histological examination. Moreover, recently, because of their indolent behavior, encapsulated FVPTC were reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and it was suggested that they represent the precursors of invasive FVPTC (NFVPTC).
AIM:The aim of the study was to characterize follicular-patterned nodules on a genetic and mRNA phenotypic point of view. In particular, we focused on NIFTPs, trying to verify whether they are a homogeneous group and whether they resemble molecularly to FAs or NFVPTCs.
METHODS: Seventy-five transcripts described as differentially expressed with a high fold change between FAs and thyroid carcinomas were selected, and tested on 19 FAs, 24 NIFTPs and 18 NFVPTCs. In addition, mutational status of BRAF (exon 15), NRAS (exons 2 and 3), HRAS (exons 2 and 3) and KRAS (exons 2 and 3) was evaluated. Uncorrelated Shrunken Centroid (USC) algorithm was used to validate clustering results.
RESULTS: Unsupervised hierarchical clustering was performed on mRNA data and two clusters were obtained. Although FAs and NFVPTCs were separate in the two clusters, NIFTPs were almost equally divided. Specifically, about half of NIFTP had a FA-like mRNA expression profile, whereas the remainder showed a NFVPTC-like profile and a higher rate of point mutation. These results were confirmed using the USC algorithm: NIFTPs were assigned as FAs or NFVPTCs strictly correlating with the genotype.
CONCLUSIONS: NIFTPs are a heterogeneous group by a genetic and mRNA phenotypic point of view. About half of them do not harbor point mutation and have a FA-like mRNA expression profile, whereas NFVPTC-like NIFTPs have a high rate of point mutation, and they likely represent the precursors of NFVPTCs.