title: RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review.
abstract: Molecular markers associated with thyroid malignancy are increasingly being used as differential diagnostic tools for thyroid nodules. However, little has been reported recently regarding the prevalence of these markers in benign lesions. The literature was systematically reviewed to examine studies that reported on the prevalence of these markers in benign thyroid lesions.
  
  
  
  Appropriate studies published between January 1, 2000, and April 30, 2015, and cataloged in PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for by combining different keywords for "thyroid tumor" with both general and specific keywords for "molecular marker" by using "AND" as the Boolean operator. All studies meeting criteria that reported the prevalence of RAS mutations, and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangements in benign thyroid lesions were included for study.
  
  
  
  A total of 64 articles (including 8162 patients, of whom 42.5% had benign lesions) that met all the study criteria were systematically reviewed and abstracted. Among 35 studies examining RAS mutations, the reported prevalence of RAS mutation in benign lesions ranged from 0% to 48%. In 38 studies examining RET/PTC rearrangements, the prevalence in benign lesions ranged from 0% to 68%. PAX8/PPAR-gamma rearrangements were examined in 27 studies, with the prevalence in benign lesions ranging from 0% to 55%.
  
  
  
  The presence of these biomarkers and the tremendous variation in reports of their prevalence in benign lesions suggests the need for caution when including these markers in diagnostic decisions. Further understanding of the importance of these markers, as well as newly discovered markers of thyroid malignancy, may be required in order to avoid overtreatment of patients with benign thyroid tumors.
authors.affiliation: 1 Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Alireza
authors.initials: A
authors.lastname: Najafian
authors.affiliation: 2 Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Salem
authors.initials: S
authors.lastname: Noureldine
authors.affiliation: 1 Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Faris
authors.initials: F
authors.lastname: Azar
authors.affiliation: 1 Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Chady
authors.initials: C
authors.lastname: Atallah
authors.affiliation: 2 Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Gina
authors.initials: G
authors.lastname: Trinh
authors.affiliation: 1 Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Schneider
authors.affiliation: 2 Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Tufano
authors.affiliation: 1 Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine , Baltimore, Maryland.|3 Department of Oncology, The Johns Hopkins University School of Medicine , Baltimore, Maryland.|4 Department of Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
mesh_terms: D015321:Gene Rearrangement; D006801:Humans; D009154:Mutation; D000072636:PAX8 Transcription Factor / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000072636:PAX8 Transcription Factor; D047495:PPAR gamma; D051096:Proto-Oncogene Proteins c-ret; D018631:ras Proteins
keywords: RAS mutations; RET/PTC and PAX8/PPAR-gamma chromosomal rearrangements; benign thyroid lesions; molecular markers; thyroid