Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier

Abstract

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%).

New Opportunities for Preoperative Diagnosis of Medullary Thyroid Carcinoma

“…A total of 555 patients were enrolled in the study. The data on 525 patients (group 1 of patients) were taken from our previous studies performed to evaluate the diagnostic accuracy of the Thyroid-INFO test [25][26][27]. In this group, in previous studies, the expression level of miRNA-375 was determined for all the samples, and, for some samples (n = 354), the basal calcitonin level was known.…”

“…A retrospective analysis of miRNA-375 expression level measured using comprehensive molecular testing (Thyroid-INFO) was carried out for group 1 patients. The test involved an analysis of expression of the GCM2 and HMGA2 genes, mRNA-146b, -221, and -375, the ratio of mitochondrial to nuclear DNA, and identification of the BRAF V600E mutation [27]. Expression of miRNA-375 was normalized to the geometric mean level of miRNA-29b, -23a, and -197.…”

MicroRNA Profile Alterations in Parathyroid Carcinoma: Latest Updates and Perspectives

“…The expression level of the GCM2 gene (glial cells missing homolog 2, a zinc finger transcription factor) was used as a marker for the detection of parathyroid cells. However, PCs were not analyzed in their study [ 36 ].…”

The Emerging Landscapes of Long Noncoding RNA in Thyroid Carcinoma: Biological Functions and Clinical Significance

“…Well-differentiated TC is composed of PTC and FTC subtypes. Approximately 80% of TCs are diagnosed as PTCs and 10% as FTCs in clinical trials worldwide (22)(23)(24)(25). According to surveillance epidemiology and end results (SEER) data from the USA, 5%-10% of TCs originate from calcitonin-producing parafollicular cells (also known as C cells) within the thyroid gland and are known as medullary TC (MTCs) (26)(27)(28)(29).…”