Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA Specimens

Abstract

Molecular markers are helpful diagnostic tools, particularly for cytologically indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation of an unambiguous surgical plan. Cycle threshold values according to the cell count for detection of the RET/PTC1 rearrangement by real-time reverse transcription-polymerase chain reaction (RT-PCR) using fresh and routine air-dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded (FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used, expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles, respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty-nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1 rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and the Nanostring showed moderate agreement with a κ value of 0.56 (p = 0.002). The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA specimen was confirmed to be technically applicable. A significant proportion (38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements.

Plasma miR-323 as a Biomarker for Screening Papillary Thyroid Cancer From Healthy Controls

“…Nonetheless, these observations necessitate the development and validation of novel non-invasive approaches to improve the disease detection in early stage and prediction of disease prognosis in PTC patients (9). Recently preoperative molecular analysis using a panel of genetic alterations emerges as a new approach to make up the limitation of FNA diagnosis (10). Therefore, it is of clinical importance to explore noninvasive biomarkers to screen patients from individuals with benign thyroid lesions.…”

Cell and Molecular Biology of Thyroid Disorders

“…Recently, various studies have focused on improving TC diagnosis with the help of molecular biological techniques. Researchers searched for thyroid-specific biomarkers and focused on cancer-specific changes in gene expression and protein content using OMICS investigations [10,11,12,13,14]. In addition, new therapeutic agents, small molecules, and antibodies have been introduced and tested in vitro, in animals, and in clinical trials [8,9].…”

Current Knowledge in Thyroid Cancer—From Bench to Bedside

“…Several manuscripts focusing on the diagnosis [ 11 , 12 , 13 , 14 , 15 ], characterisation [ 16 , 17 , 18 , 19 ], and treatment [ 20 , 21 , 22 ] of thyroid cancer, as well as on alterations of thyroid cancer cells by altered gravity [ 23 , 24 ] or radiation damage of the thyroid gland [ 25 ], including genetics, proteomics, molecular, and cell biology, are published in this Special Issue. In addition, an original publication reports that the polymorphism loci of the tumour necrosis factor superfamily member 4 ( TNFSF4 ) gene is related to early-onset autoimmune thyroid diseases [ 26 ].…”

“…Ko et al [ 12 ] showed that the diagnostic limitation of FNA on indeterminate nodules might be partially overcome by a molecular analysis before surgery. RET/PTC1 rearrangement by RT-PCR analysis on air-dried FNA specimens could be technically applicable.…”

“…A significant proportion (38.2%) of the BRAF and RAS wild type PTCs harbour a RET/PTC1 rearrangement. This preoperative molecular analysis is a helpful diagnostic examination of FNA specimens to characterise indeterminate thyroid nodules [ 12 ].…”