Elsevier

Endocrine Practice

Volume 23, Issue 8, August 2017, Pages 979-989
Endocrine Practice

Review Articles
Role of Molecular Markers in Thyroid Nodule Management: Then and Now

https://doi.org/10.4158/EP171805.RAGet rights and content

ABSTRACT

Objective: To describe the evolution and clinical utility of molecular testing for thyroid nodules and cancer achieved over the last 2 decades.

Methods: Scientific reports on thyroid cancer genetics and molecular diagnostics in thyroid nodules.

Results: Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules.

Conclusion: The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients.

Abbreviations: FNA = fine-needle aspiration miRNA = micro RNA NGS = next-generation sequencing NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features NPV = negative predictive value PPV = positive predictive value PTC = papillary thyroid carcinoma RAI = radioactive iodine

Section snippets

Clinical Challenges

Thyroid nodules are common, particularly in women and with increased age. Close to 50% of individuals over the age of 60 have nodules detectable by ultrasound and 5% by palpation (1–3). However, the incidence of cancer in these nodules is low, with only 5 to 15% of medically evaluated thyroid nodules found to be malignant (4–6). Distinguishing benign from malignant disease is typically achieved by fine-needle aspiration (FNA) biopsy and cytologic evaluation of nodules that are selected for

Genetic Basis of Thyroid Cancer: New Discoveries and Concepts

Over the last several decades, our understanding of the genetic mechanisms of thyroid cancer has expanded dramatically. Recent discoveries have been powered by next-generation sequencing (NGS), a revolutionary technology that enables researchers to obtain genetic information on tens and hundreds of genes in one assay using a small amount of cells collected from the lesion. A recent study from The Cancer Genome Atlas provided comprehensive genetic characterization of papillary thyroid carcinoma

Progress in Diagnostic Molecular Markers for Thyroid Nodules

Progress in the application of molecular markers to cancer diagnosis in thyroid nodules parallels the expansion of knowledge on genetic mechanisms of thyroid cancer and introduction of high-throughput genotyping techniques (Fig. 4). It was first demonstrated in the early 1990s that material collected from a thyroid nodule by FNA provides a sufficient amount of cells to detect individual point mutations (27) or gene fusions (28). However, it was not until the identification of BRAF mutations in

Utility of Genetic Markers for Cancer Prognostication

For thyroid nodules with high probability of malignancy, the pre-operative assessment of cancer aggressiveness can help select the most appropriate surgical and post-surgical management. Many patients with thyroid cancer have indolent disease and are at low risk for disease recurrence after cancer removal. These patients can be treated by lobectomy and are unlikely to benefit from RAI ablation and TSH suppression (16,48). Similarly, surgical excision of a pre-cancer tumor, NIFTP, by lobectomy

SUMMARY: Towards More Tailored Patient Management Based on the Combination of Cytology and Molecular Testing

Advances in our understanding of the genetics of thyroid cancer along with the availability of new DNA sequencing technologies have propelled the development of several molecular tests for thyroid nodules and cancer. The primary purpose of these tests is to assess the probability of cancer in thyroid nodules with indeterminate cytology (Table 2). Moreover, multigene panels also provide valuable prognostic information that becomes available preoperatively. Specifically, thyroid nodules with

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    DISCLOSURE

    Dr. Nikiforov is a consultant for Quest Diagnostics and owner of intellectual property related to ThyroSeq. In addition, his employer, University of Pittsburg Medical Center, has a contract with CBLPath to offer ThyroSeq test commercially.

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