title: Molecular-Directed Treatment of Differentiated Thyroid Cancer: Advances in Diagnosis and Treatment.
abstract: Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer.
  
  
  
  To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer.
  
  
  
  A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only.
  
  
  
  Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer.
  
  
  
  Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.
authors.affiliation: Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Linwah
authors.initials: L
authors.lastname: Yip
authors.affiliation: Section of Endocrine Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina3Duke Clinical Research Institute, Durham, North Carolina4Deputy Editor, JAMA Surgery.
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Sosa
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D011379:Prognosis; D018570:Risk Assessment; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D013965:Thyroidectomy
chemical_list: D014408:Biomarkers, Tumor