Review ArticlesRole of Molecular Markers in Thyroid Nodule Management: Then and Now
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
REFERENCES (65)
Changing trends in thyroid practice: understanding nodular thyroid disease
Endocr Pract
(2004)- et al.
A genetic model for colorectal tumorigenesis
Cell
(1990) - et al.
Diagnostic value of fine needle aspiration BRAF(V600E) mutation analysis in papillary thyroid cancer: a systematic review and meta-analysis
Hum Pathol
(2015) - et al.
False-positive FNA due to highly sensitive BRAF assay
Endocr Pract
(2014) Management of a solitary thyroid nodule
N Engl J Med
(1993)- et al.
Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination
Eur J Clin Invest
(2009) - et al.
Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography
J Clin Endocrinol Metab
(2006) - et al.
High prevalence of carcinoma in ultrasonography-guided fine needle aspiration cytology of thyroid nodules
Endocr J
(2008) - et al.
Prevalence of thyroid cancer in multinodular goiter versus single nodule: a systematic review and meta-analysis
Thyroid
(2013) - et al.
The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis
Acta Cytol
(2012)
The Bethesda System for Reporting Thyroid Cytopathology
Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference
Diagn Cytopathol
Incidence trends for papillary thyroid carcinoma and their correlation with thyroid surgery and thyroid fine-needle aspirate cytology
Thyroid
Increasing incidence of thyroid cancer in the United States, 1973–2002
JAMA
Annual financial impact of well-differentiated thyroid cancer care in the United States
Cancer
Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis
Health Aff (Millwood)
Outcomes of patients with differentiated thyroid cancer risk-stratified according to the American Thyroid Association and Latin American Thyroid Society risk of recurrence classification systems
Thyroid
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
Integrated genomic characterization of papillary thyroid carcinoma
Cell
Identification of driving ALK fusion genes and genomic landscape of medullary thyroid cancer
PLoS Genet
Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing
Hum Mol Genet
Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers
J Clin Invest
Progesterone signalling in breast cancer: a neglected hormone coming into the limelight
Nat Rev Cancer
Pathogenetic mechanisms in thyroid follicular-cell neoplasia
Nat Rev Cancer
Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors
JAMA Oncol
Changing the cancer diagnosis: the case of follicular variant of papillary thyroid cancer-primum, non nocere and NIFTP
Thyroid
Thyroid gland clonality revisited: the embryonal patch size of the normal human thyroid gland is very large, suggesting X-chromosome inactivation tumor clonality studies of thyroid tumors have to be interpreted with caution
J Clin Endocrinol Metab
PCR amplification and analysis of ras oncogenes from thyroid cytologic smears
Diagn Mol Pathol
Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer
J Clin Endocrinol Metab
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma
Cancer Res
BRAF mutation in papillary thyroid carcinoma
J Natl Cancer Inst
Cited by (0)
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.