Molecular markers in thyroid cytology: diagnostic and prognostic implications

Abstract

The discovery of thyroid nodules in the general population has risen markedly with the greater use of ultrasound resulting in increasing use of ultrasound-guided fine needle aspiration (FNA) biopsy. Although FNA can identify the majority of nodules as either benign or malignant, one-third of aspirates demonstrate indeterminate cytologic characteristics. Though most of these nodules will be pathologically benign, thyroid surgery has usually been needed to make an accurate diagnosis, and the extent of surgery needed (lobectomy versus total thyroidectomy) is difficult to predict in advance. New molecular techniques are being investigated and used clinically to improve decision making in patients with thyroid nodules with indeterminate cytology. These molecular markers have the potential to help clinicians decide which patients may be monitored without thyroid surgery, and also the optimal strategy when surgery is felt to be necessary.

Keywords::

• genetic markers
• indeterminate thyroid cytology
• molecular markers
• mutation panel
• thyroid cancer
• thyroid nodules

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The Incidence of nodular thyroid disease and thyroidcancer has been increasing over the past two decades due to the increasing use of high-frequency neck US. Mortality from thyroid cancer continues to be low (survival rate of nearly 100% for localized disease) [49]. Risk stratification of thyroid nodules is of paramount importance to identify those patients who are most likely to benefit from intervention. Management of patient with indeterminate nodules remains problematic. Using cytology and clinical factors alone, most patients will be recommended for surgery, even though only a minority will have thyroid cancers on final pathology. Molecular markers are being intensively investigated to refine management of these patients.

• • Currently, commercially available molecular markers for thyroid cytology include Afirma®, TSHR mRNA and miRInform® mutation panel.

• • Mutation analysis panel (BRAFV600 E, NRAS codon 61, HRAS codon 61, KRAS codons 12/13 point mutations and RET/PTC 1, RET/PTC 2, RET/PTC 3 and PAX8/PPAR γ) shows a very high positive predictive value for thyroid cancer, but the sensitivity is low. These tests can be used to guide surgical extent, but cannot be used to exclude malignancy.

• • Genetic expression analysis identifies nodules that are likely to be benign with a high negative predictive value. This test has the potential to reduce the number of unnecessary surgical procedure in patients with indeterminate cytology.

Notes