title: Benign thyroid nodules with RAS mutation grow faster.
abstract: BACKGROUND
  The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules.
  
  
  OBJECTIVE
  The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation.
  
  
  METHODS
  Genomic DNA obtained by fine-needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS(61) and KRAS(13) mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation.
  
  
  RESULTS
  A RAS mutation was found in 24 thyroid aspirates (30·8%, 8 NRAS(61) and 16 KRAS(13) ). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0·017). After a 25-month mean follow-up, RAS mutation-positive nodules displayed faster growth (RAS mutation-positive vs RAS mutation-negative % annual growth 27·6% ±32·2% vs 1·0% ±17·0%, P < 0·001).
  
  
  CONCLUSIONS
  Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild-type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management.
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Puzziello
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Guerra
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Murino
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Izzo
authors.affiliation: Endocrinology, AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Carrano
authors.affiliation: Endocrinology, AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Angrisani
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Pio
authors.initials: P
authors.lastname: Zeppa
authors.affiliation: Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marotta
authors.affiliation: Department of Clinical Medicine and Surgery, University 'Federico II', Naples, Italy.
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
mesh_terms: D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)