Molecular Classification of Thyroid Nodules with Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides

Autor(es)

dos Santos, Marcos Tadeu ^{[1, 2]} ; Buzolin, Ana Ligia ^[2] ; Gama, Ricardo Ribeiro ^{[3, 1]} ; Albino da Silva, Eduardo Caetano ^[4] ; Dufloth, Rozany Mucha ^[4] ; Alves Figueiredo, David Livingstone ^[5] ; Carvalho, Andre Lopes ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[2] Onkos Mol Diagnost, Dept Res & Dev, 1805 Ave Doutora Nadir Aguiar, BR-14056680 Ribeirao Preto, SP - Brazil

^[3] Barretos Canc Hosp, Dept Head & Neck Surg, Barretos, SP - Brazil

^[4] Barretos Canc Hosp, Dept Pathol, Barretos, SP - Brazil

^[5] Midwestern State Univ UNICTR, Guarapuava, PR - Brazil

• Tipo de documento: Artigo Científico
• Fonte: THYROID; v. 28, n. 12 NOV 2018.
• Citações Web of Science: 4

Resumo

Background: Thyroid nodules can be identified in up to 68% of the population. Fine-needle aspiration (FNA) cytopathology classifies 20%-30% of nodules as indeterminate, and these are often referred for surgery due to the risk of malignancy. However, histological postsurgical reports indicate that up to 84% of cases are benign, highlighting a high rate of unnecessary surgeries. We sought to develop and validate a microRNA (miRNA)-based thyroid molecular classifier for precision endocrinology (mir-THYpe) with both high sensitivity and high specificity, to be performed on the FNA cytology smear slide with no additional FNA. Methods: The expression of 96 miRNA candidates from 39 benign/39 malignant thyroid samples, (indeterminate on FNA) was analyzed to develop and train the mir-THYpe algorithm. For validation, an independent set of 58 benign/37 malignant FNA smear slides (also classified as indeterminate) was used. Results: In the training set, with a 10-fold cross-validation using only 11 miRNAs, the mir-THYpe test reached 89.7% sensitivity, 92.3% specificity, 90.0% negative predictive value and 92.1% positive predictive value. In the FNA smear slide validation set, the mir-THYpe test reached 94.6% sensitivity, 81.0% specificity, 95.9% negative predictive value, and 76.1% positive predictive value. Bayes' theorem shows that the mir-THYpe test performs satisfactorily in a wide range of cancer prevalences. Conclusions: The presented data and comparison with other commercially available tests suggest that the mir-THYpe test can be considered for use in clinical practice to support a more informed clinical decision for patients with indeterminate thyroid nodules and potentially reduce the rates of unnecessary thyroid surgeries. (AU)

• Processo FAPESP: 15/07590-3 - Classificação molecular de nódulos tireoidianos indeterminados através de microRNA profiling
• Beneficiário: Marcos Tadeu dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE