Malignant risk stratification of thyroid FNA specimens with indeterminate cytology based on molecular testing.
BACKGROUND
Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations.


METHODS
This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology.


RESULTS
A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability.


CONCLUSIONS
One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery.
Institute for the Application of Nuclear Energy, Department of Endocrinology and Radioimmunology, University of Belgrade, Belgrade, Serbia.
Svetlana
S
Paskaš
Institute for the Application of Nuclear Energy, Department of Endocrinology and Radioimmunology, University of Belgrade, Belgrade, Serbia.
Jelena
J
Janković
Center for Endocrine Surgery, Institute of Endocrinology, Diabetes, and Diseases of Metabolism, University of Belgrade, Belgrade, Serbia.
Vladan
V
Živaljević
Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia.
Svetislav
S
Tatić
Department of Endocrine and Cardiovascular Pathology, Clinical Center of Serbia, Belgrade, Serbia.
Vesna
V
Božić
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Aleksandra
A
Nikolić
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Dragica
D
Radojković
Institute for the Application of Nuclear Energy, Department of Endocrinology and Radioimmunology, University of Belgrade, Belgrade, Serbia.
Svetlana
S
Savin
Institute for the Application of Nuclear Energy, Department of Endocrinology and Radioimmunology, University of Belgrade, Belgrade, Serbia.
Dubravka
D
Cvejić
D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D044963:Biopsy, Fine-Needle / Q000379:methods; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003581:Cytodiagnosis / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology*
D014408:Biomarkers, Tumor; D037502:Galectin 3; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF; fine-needle aspirates; galectin-3; indeterminate cytology; microRNA 221 (miR-221); microRNA 222 (miR-222); thyroid cancer