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

Aarti Mathur, Julie Weng, Willieford Moses, Seth M. Steinberg, Reza Rahabari, Mio Kitano, Elham Khanafshar, Britt Marie Ljung, Quan Yang Duh, Orlo H. Clark, Electron Kebebew

Research output: Contribution to journalArticle

Abstract

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1170-1176
Number of pages7
JournalSurgery
Volume148
Issue number6
DOIs
StatePublished - Dec 2010
Externally publishedYes

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Fine Needle Biopsy
Thyroid Gland
Prospective Studies
Cell Biology
Tissue Inhibitor of Metalloproteinase-1
Mutation
Neoplasms
Thyroidectomy
Thyroid Neoplasms
Multivariate Analysis
Biomarkers
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Surgery

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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. / Mathur, Aarti; Weng, Julie; Moses, Willieford; Steinberg, Seth M.; Rahabari, Reza; Kitano, Mio; Khanafshar, Elham; Ljung, Britt Marie; Duh, Quan Yang; Clark, Orlo H.; Kebebew, Electron.

In: Surgery, Vol. 148, No. 6, 12.2010, p. 1170-1176.

Research output: Contribution to journalArticle

Mathur, A, Weng, J, Moses, W, Steinberg, SM, Rahabari, R, Kitano, M, Khanafshar, E, Ljung, BM, Duh, QY, Clark, OH & Kebebew, E 2010, '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', Surgery, vol. 148, no. 6, pp. 1170-1176. https://doi.org/10.1016/j.surg.2010.09.025
Mathur, Aarti ; Weng, Julie ; Moses, Willieford ; Steinberg, Seth M. ; Rahabari, Reza ; Kitano, Mio ; Khanafshar, Elham ; Ljung, Britt Marie ; Duh, Quan Yang ; Clark, Orlo H. ; Kebebew, Electron. / 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. In: Surgery. 2010 ; Vol. 148, No. 6. pp. 1170-1176.
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abstract = "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. Conclusion: 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.",
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AU - Mathur, Aarti

AU - Weng, Julie

AU - Moses, Willieford

AU - Steinberg, Seth M.

AU - Rahabari, Reza

AU - Kitano, Mio

AU - Khanafshar, Elham

AU - Ljung, Britt Marie

AU - Duh, Quan Yang

AU - Clark, Orlo H.

AU - Kebebew, Electron

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N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

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