임상적 치료 결정을 위한 갑상선 미결정 결절의 분자 표지자 검사
Molecular Testing of Thyroid Indeterminate Nodules for Clinical Management Decision
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초록
Thyroid nodules are the most common endocrine tumor. Ultrasonography and fine-needle aspiration (FNA) are currently accurate diagnostic tools for evaluating thyroid nodules. However, 10-30% of FNA specimens are cytologically indeterminate. Making an accurate diagnosis between benign and malignant nodules is important so that patients with malignant nodule receive proper treatment and patients with benign nodule can avoid unnecessary treatment. Several genetic changes such as point mutations of the BRAF or RAS and rearrangements of the RET/PTC1, RET/PTC3, PAX8/PPARY are used to adjust to indeterminate FNA. Such a mutational analysis has an excellent positive predictive value (PPV), but there is a weakness in the low negative predictive value (NPV). Gene-expression classifier (GEC) has been found helpful in identify nodules that are benign rather than malignant. GEC has an excellent NPV, but there is a weakness of low PPV. Multiplatform mutational and miRNA test (MPT) and next-generation sequencing assay (NGS) are being studied to compensate for these weaknesses. Molecular tests appear to be a good solution for improving the accuracy of indeterminate FNA cytology specimens and support the clinical management decisions in patients with indeterminate cytologic nodules, but further prospective multicenter trials are required for validation of reported findings and need evaluation of cost-effectiveness. This paper will review recently available molecular diagnostic tools of thyroid nodule.
Abstract
Thyroid nodules are the most common endocrine tumor. Ultrasonography and fine-needle aspiration (FNA) are currently accurate diagnostic tools for evaluating thyroid nodules. However, 10-30% of FNA specimens are cytologically indeterminate. Making an accurate diagnosis between benign and malignant nodules is important so that patients with malignant nodule receive proper treatment and patients with benign nodule can avoid unnecessary treatment. Several genetic changes such as point mutations of the BRAF or RAS and rearrangements of the RET/PTC1, RET/PTC3, PAX8/PPARY are used to adjust to indeterminate FNA. Such a mutational analysis has an excellent positive predictive value (PPV), but there is a weakness in the low negative predictive value (NPV). Gene-expression classifier (GEC) has been found helpful in identify nodules that are benign rather than malignant. GEC has an excellent NPV, but there is a weakness of low PPV. Multiplatform mutational and miRNA test (MPT) and next-generation sequencing assay (NGS) are being studied to compensate for these weaknesses. Molecular tests appear to be a good solution for improving the accuracy of indeterminate FNA cytology specimens and support the clinical management decisions in patients with indeterminate cytologic nodules, but further prospective multicenter trials are required for validation of reported findings and need evaluation of cost-effectiveness. This paper will review recently available molecular diagnostic tools of thyroid nodule.
참고문헌 (24)
- Mazzaferri EL, "Management of a solitary thyroid nodule", N Engl J Med, 328(8), pp.553~559 (1993)
- Gharib H, "Fine-needle aspiration biopsy of the thyroid: An appraisal", Ann Intern Med, 118(4), pp.282~289 (1993)
- Cibas ES, "The Bethesda system for reporting thyroid cytopathology", Am J Clin Pathol, 132(5), pp.658~665 (2009)
- Horne MJ, "Thyroid follicular lesion of undetermined significance: Evaluation of the risk of malignancy using the two-tier sub-classification", Diagn Cytopathol, 40(5), pp.410~415 (2012)
- Haugen BR, "2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer", Thyroid, 26(1), pp.1~133 (2016)
- 이가희, "2016년 대한갑상선학회 갑상선결절 및 암 진료 권고안 개정안", International Journal of Thyroidology, 9(2), pp.59~126 (2016), 대한갑상선학회
- Nikiforova MN, "Molecular diagnostics and predictors in thyroid cancer", Thyroid, 19(12), pp.1351~1361 (2009)
- Adeniran AJ, "BRAF mutation testing of thyroid fine-needle aspiration specimens enhances the predictability of malignancy in thyroid follicular lesions of undetermined significance", Acta Cytol, 55(6), pp.570~575 (2011)
- Mekel M, "Surgical implications of B-RafV600E mutation in fine-needle aspiration of thyroid nodules", Am J Surg, 200(1), pp.136~143 (2010)
- Kim SK, "Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status", J Clin Endocrinol Metab, 96(3), pp.658~664 (2011)
- Liu X, "Highly prevalent TERT promoter mutations in aggressive thyroid cancers", Endocr Relat Cancer, 20(4), pp.603~610 (2013)
- Liu R, "Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy", Endocr Relat Cancer, 21(5), pp.825~830 (2014)
- Patel SG, "Preoperative detection of RAS mutation may guide extent of thyroidectomy", Surgery, 161(1), pp.168~175 (2017)
- Paulson VA, "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features accounts for more than half of "carcinomas" harboring RAS mutations", Thyroid, 27(4), pp.506~511 (2017)
- Nikiforov YE, "Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples", J Clin Endocrinol Metab, 96(11), pp.3390~3397 (2011)
- Nikiforov YE, "Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules", J Clin Endocrinol Metab, 94(6), pp.2092~2098 (2009)
- Alexander EK, "Preoperative diagnosis of benign thyroid nodules with indeterminate cytology", N Engl J Med, 367(8), pp.705~715 (2012)
- Duick DS, "The impact of benign gene expression classifier test results on the endocrinologist-patient decision to operate on patients with thyroid nodules with indeterminate fine-needle aspiration cytopathology", Thyroid, 22(10), pp.996~1001 (2012)
- Alexander EK, "Multicenter clinical experience with the Afirma gene expression classifier", J Clin Endocrinol Metab, 99(1), pp.119~125 (2014)
- Labourier E, "Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology", J Clin Endocrinol Metab, 100(7), pp.2743~2750 (2015)
- Nikiforov YE, "Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm", suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay, 2014, pp.120(23), 3627~3634
- Gupta N, "RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers", J Clin Endocrinol Metab, 98(5), pp.E914~E922 (2013)
- Lee L, "Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology", J Clin Endocrinol Metab, 99(8), pp.2674~2682 (2014)
- Wu JX, "Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules", Surgery, 159(1), pp.118~126 (2016)