title: Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings.
abstract: BACKGROUND
  Fine-needle aspiration biopsy (FNAB) is the primary means to distinguish benign from malignant nodules and select patients for surgery. However, adjunctive diagnostic tests are needed because in 20-40% of cases the FNAB result is uncertain.
  
  
  OBJECTIVE
  We investigated whether a search for the oncogenes RET/PTC, TRK and BRAF(V600E) in thyroid aspirates could refine an uncertain diagnosis.
  
  
  METHODS
  A total of 132 thyroid aspirates, including colloid nodules, inadequate samplings, indeterminate and suspicious for malignancy were analysed by reverse transcription polymerase chain reaction (RT-PCR) and mutant allele-specific amplification techniques for the presence of oncogenes.
  
  
  RESULTS
  No oncogenes were detected in 48 colloid nodules, 46 inadequate and 19 indeterminate FNABs, then confirmed to be benign at histology. No oncogenes were detected in one follicular thyroid cancer (FTC) with indeterminate cytology. Five out of six papillary thyroid cancers (83%) with FNAB suspicious for malignancy were correctly diagnosed by the presence of oncogenes. Among these, four (67%) contained the BRAF mutation and one (17%) contained RET/PTC-3. On final analysis, no false-positive results were reported in 131 samples and five out of seven carcinomas (71%) were correctly diagnosed. The finding of oncogenes in FNAB specimens suspicious for malignancy guided the extent of surgical resection, changing the surgery from diagnostic to therapeutic in five cases.
  
  
  CONCLUSIONS
  Detection of RET/PTC, TRK and BRAF(V600E) in FNAB specimens is proposed as a diagnostic adjunctive tool in the evaluation of thyroid nodules with suspicious cytological findings.
authors: Department of Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy.
authors: Maria Rosaria
authors: MR
authors: Sapio
authors: Daniela
authors: D
authors: Posca
authors: Angelo
authors: A
authors: Raggioli
authors: Anna
authors: A
authors: Guerra
authors: Vincenzo
authors: V
authors: Marotta
authors: Maurilio
authors: M
authors: Deandrea
authors: Manuela
authors: M
authors: Motta
authors: Paolo Piero
authors: PP
authors: Limone
authors: Giancarlo
authors: G
authors: Troncone
authors: Alessia
authors: A
authors: Caleo
authors: Guido
authors: G
authors: Rossi
authors: Gianfranco
authors: G
authors: Fenzi
authors: Mario
authors: M
authors: Vitale
mesh_terms: D001707:Biopsy, Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D015321:Gene Rearrangement; D006801:Humans; D009857:Oncogenes; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology
chemical_list: D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf