A prospective study evaluating the accuracy of using combined clinical factors and candidate diagnostic markers to refine the accuracy of thyroid fine needle aspiration biopsy.
BACKGROUND
Approximately 30% of fine needle aspiration biopsies of the thyroid have inconclusive results. We conducted a prospective trial to determine whether clinical and molecular markers could be used in combination to improve the accuracy of thyroid fine needle aspiration biopsy.


METHODS
Clinical, tumor genotyping for common somatic mutations (BRAF V600E, NRAS, KRAS, RET/PTC1, RET/PTC3, and NTRK1), and the gene expression levels of 6 candidate diagnostic markers were analyzed by univariate and multivariate methods in 341 patients to determine whether they could distinguish reliably benign from malignant thyroid neoplasms, and a scoring model was derived.


RESULTS
By a multivariate analysis, fine needle aspiration biopsy cytology classification, the presence of a NRAS mutation, and the tissue inhibitor of metalloproteinase 1 expression level were associated jointly with malignancy. The overall accuracy of the scoring model, including these 3 variables, to distinguish benign from malignant thyroid tumors was 91%, including 67% for the indeterminate and 77% for the suspicious FNA subgroups.


CONCLUSIONS
Fine needle aspiration biopsy cytology classification, the presence of NRAS mutation, and tissue inhibitor of metalloproteinase 1 messenger RNA expression levels in combination provide a greater diagnostic accuracy than fine needle aspiration biopsy cytology alone to allow selection of more definitive initial operative treatment. The sensitivity of the scoring model, however, was too low to avoid the need for diagnostic thyroidectomies for indeterminate fine needle aspiration biopsy findings.
Endocrine Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, MD, USA.
Aarti
A
Mathur
Julie
J
Weng
Willieford
W
Moses
Seth M
SM
Steinberg
Reza
R
Rahbari
Reza
R
Rahabari
Mio
M
Kitano
Elham
E
Khanafshar
Britt-Marie
BM
Ljung
Quan-Yang
QY
Duh
Orlo H
OH
Clark
Electron
E
Kebebew
D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle / Q000379:methods*; D003937:Diagnosis, Differential; D005006:Ethnicity; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011446:Prospective Studies; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015203:Reproducibility of Results; D013959:Thyroid Diseases / Q000473:pathology* / Q000601:surgery; D013961:Thyroid Gland / Q000166:cytology / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy / Q000706:statistics & numerical data
D012334:RNA, Neoplasm; D012313:RNA