title: PREDICTIVE VALUE OF SOMATIC MUTATIONS FOR THE DEVELOPMENT OF MALIGNANCY IN THYROID NODULES BY CYTOPATHOLOGY.
abstract: OBJECTIVE
  The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy.
  
  
  METHODS
  A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology.
  
  
  RESULTS
  In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%.
  
  
  CONCLUSIONS
  Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value.
  
  
  BACKGROUND
  BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.
authors.forename: Csaba
authors.initials: C
authors.lastname: Halászlaki
authors.forename: Bálint
authors.initials: B
authors.lastname: Tóbiás
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.forename: János P
authors.initials: JP
authors.lastname: Kósa
authors.forename: János
authors.initials: J
authors.lastname: Horányi
authors.forename: Eszter
authors.initials: E
authors.lastname: Bölöny
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Nagy
authors.forename: Gábor
authors.initials: G
authors.lastname: Speer
authors.forename: Balázs
authors.initials: B
authors.lastname: Járay
authors.forename: Eszter
authors.initials: E
authors.lastname: Székely
authors.forename: Roland
authors.initials: R
authors.lastname: Istók
authors.forename: Tamás
authors.initials: T
authors.lastname: Székely
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Putz
authors.forename: Magdolna
authors.initials: M
authors.lastname: Dank
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.forename: István
authors.initials: I
authors.lastname: Takács
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003581:Cytodiagnosis; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D060888:Real-Time Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult