Digital Gene Expression Analysis on Cytology Smears Can Rule Out Malignancy in Follicular-Patterned Thyroid Tumors

Abstract

it.Patients with indeterminate thyroid nodules (Bethesda III and IV) are often treated with diagnostic lobectomy, which in most cases represents an overtreatment. A reliable rule-out molecular test could spare patients unnecessary surgery. Stained smears of 88 indeterminate thyroid nodules with histologic diagnosis of follicular-patterned tumors were selected: 34 follicular adenomas (FAs), 34 follicular variant papillary thyroid carcinomas (FVPTCs), and 20 noninvasive follicular neoplasms with papillarylike nuclear features (NIFTPs). The expression level of 126 genes was measured by digital counting. Mutation testing was performed for the main gene mutations and fusions. Performance of gene expression and mutation tests was calculated by receiver operating characteristic analysis. The gene expression model showed an area under the curve (AUC) of 88%, with 91% negative predictive value in FAs and FVPTCs only. Part of NIFTPs was labeled as benign, and part was labeled as malignant; thus, the classifier performance worsened. Two FAs (5.9%), eight NIFTPs (40%), and 22 FVPTCs (64.7%) were mutation positive. Mutation testing AUC was 79% in FAs and FVPTCs, and decreased by including NIFTPs. This gene expressionebased test was feasible in thyroid-stained smears, showed higher AUC than mutation test, and had a high negative predictive valuedmaking it a good candidate as a rule-out test for indeterminate thyroid cytology. NIFTPs have a heterogeneous phenotype, and their preoperative diagnosis requires further investigation.

GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

“…Gene expression profiling has been widely evaluated in thyroid cancer for biomarker discovery, especially for diagnostic purposes (14)(15)(16)(17). Transcriptomic-based studies have revealed predictors candidates of prognosis, including overexpression of MUC1 (18), MEDAG (19), and SPHK1 (20), and downexpression of FMO1 (21), and FOXF1 (22).…”

Automated diagnosis and management of follicular thyroid nodules based on the devised small-datasets interpretable foreground optimization network deep learning: A multicenter diagnostic study

“…Few previous studies were carried out on differential diagnosis of FTC and FA, most of which focused on improvements in diagnosis methods in cytology or pathology 6 , 7 , 36 . Our study exhibited a noninvasive, high-precision preoperative predicting system on follicular thyroid neoplasms for the first time.…”

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

“…However, authors mostly focused on differential miRNA expression between malignant and benign tumors, without considering the presence of RAS mutations as a confounding factor [ 24 – 26 ]; on the contrary, several miRNAs are known to be specifically deregulated in BRAF mutant thyroid tumors compared to wild-type cases [ 27 , 28 ]. In previous studies from our group, we demonstrated that wild-type NIFTPs show a benign-like miRNA phenotype, while RAS -mutant NIFTPs show a malignant-like miRNA phenotype [ 29 , 30 ]; in detail, 12 miRNAs were significantly deregulated in mutant versus wild-type NIFTPs ( miR-221-5p , miR-221-3p , miR-222-3p , miR-146b-5p , miR-181a-3p , miR-28-5p , miR-363-3p , miR-342-3p , miR-1285-5p , miR-152-3p , miR-25-3p , miR-30e-3p ) [ 30 ]. Likewise, comparing RAS -negative and RAS -mutant FAs, herein we report 12 differentially expressed miRNAs, whose deregulation is likely related to RAS mutations ( miR-222-3p , miR-7-5p , miR-221-3p , miR-221-5p , miR-19a-3p , miR-135a-5p , miR-146b-5p , let-7a-5p , miR-92a-3p , miR-142-3p , miR-296-5p , miR-26a-5p ).…”