Guido Fadda1, Sebastiano Filetti2, Marialuisa Sponziello2, Chiara Brunelli1, Antonella Verrienti3, Giorgio Grani2, Valeria Pecce2, Luana Abballe2, Valeria Ramundo2, Giuseppe Damante4, Diego Russo5, Celestino Pio Lombardi6, Cosimo Durante2, Esther Diana Rossi1, Patrizia Straccia1. 1. Division of Anatomic Pathology and Histology, Catholic University of Sacred Heart, Foundation "Agostino Gemelli" University Hospital, Rome, Italy. 2. Department of Translational and Precision Medicine, "Sapienza" University of Rome, 00161, Rome, Italy. 3. Department of Translational and Precision Medicine, "Sapienza" University of Rome, 00161, Rome, Italy. antonella.verrienti@uniroma1.it. 4. Department of Medicine, University of Udine, 33100, Udine, Italy. 5. Department of Health Sciences, "Magna Graecia" University of Catanzaro, 88100, Catanzaro, Italy. 6. Division of Endocrine Surgery, Catholic University of Sacred Heart, Foundation "Agostino Gemelli" University Hospital, Rome, Italy.
Abstract
PURPOSE: Deciding whether patients with a cytologically indeterminate thyroid nodule should be referred for surgery or for active surveillance is an important challenge for clinicians. The aim of this study was to evaluate the performance of a novel dual-component molecular assay as an ancillary molecular method for resolving indeterminate thyroid nodule cytology. METHODS: We selected 156 thyroid nodules from those that had undergone fine-needle aspiration processed by liquid-based cytology and surgical resection between June 2016 and December 2017. The sample set included 63 nodules cytologically classified as indeterminate, and 93 other nodules randomly selected from those with non-diagnostic, benign, suspicious, or malignant cytology. Nucleic acids from each nodule were subjected to next-generation sequencing analysis for mutation detection in 23 genes and to digital polymerase chain reaction (PCR) evaluation for miR-146b-5p expression levels. RESULTS: Used alone, mutation analysis in the indeterminate subset (cancer prevalence: 22.5%) displayed high sensitivity (89%) and NPV (96%). In contrast, the miR-146b-5p assay offered high specificity (93%) and PPV (93%). Combined use of both analyses improved panel performance by eliminating false-negative results. CONCLUSIONS: These preliminary data suggest that a dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign. If these findings are confirmed, this test can be considered for use in clinical practice and is expected to reduce diagnostic surgery and health care costs, and to improve patient quality of life.
PURPOSE: Deciding whether patients with a cytologically indeterminate thyroid nodule should be referred for surgery or for active surveillance is an important challenge for clinicians. The aim of this study was to evaluate the performance of a novel dual-component molecular assay as an ancillary molecular method for resolving indeterminate thyroid nodule cytology. METHODS: We selected 156 thyroid nodules from those that had undergone fine-needle aspiration processed by liquid-based cytology and surgical resection between June 2016 and December 2017. The sample set included 63 nodules cytologically classified as indeterminate, and 93 other nodules randomly selected from those with non-diagnostic, benign, suspicious, or malignant cytology. Nucleic acids from each nodule were subjected to next-generation sequencing analysis for mutation detection in 23 genes and to digital polymerase chain reaction (PCR) evaluation for miR-146b-5p expression levels. RESULTS: Used alone, mutation analysis in the indeterminate subset (cancer prevalence: 22.5%) displayed high sensitivity (89%) and NPV (96%). In contrast, the miR-146b-5p assay offered high specificity (93%) and PPV (93%). Combined use of both analyses improved panel performance by eliminating false-negative results. CONCLUSIONS: These preliminary data suggest that a dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign. If these findings are confirmed, this test can be considered for use in clinical practice and is expected to reduce diagnostic surgery and health care costs, and to improve patient quality of life.
Authors: Iñigo Landa; Tihana Ibrahimpasic; Laura Boucai; Rileen Sinha; Jeffrey A Knauf; Ronak H Shah; Snjezana Dogan; Julio C Ricarte-Filho; Gnana P Krishnamoorthy; Bin Xu; Nikolaus Schultz; Michael F Berger; Chris Sander; Barry S Taylor; Ronald Ghossein; Ian Ganly; James A Fagin Journal: J Clin Invest Date: 2016-02-15 Impact factor: 14.808
Authors: Zubair W Baloch; Virginia A LiVolsi; Syl L Asa; Juan Rosai; Maria J Merino; Gregory Randolph; Philippe Vielh; Richard M DeMay; Mary K Sidawy; William J Frable Journal: Diagn Cytopathol Date: 2008-06 Impact factor: 1.582
Authors: Cosimo Durante; Giorgio Grani; Livia Lamartina; Sebastiano Filetti; Susan J Mandel; David S Cooper Journal: JAMA Date: 2018-03-06 Impact factor: 56.272