title: Preoperative detection of RAS mutation may guide extent of thyroidectomy.
abstract: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy.
  
  
  
  Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay.
  
  
  
  In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease.
  
  
  
  Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.
authors.affiliation: Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.affiliation: Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Carty
authors.affiliation: Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: McCoy
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: N Paul
authors.initials: NP
authors.lastname: Ohori
authors.affiliation: Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Shane O
authors.initials: SO
authors.lastname: LeBeau
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.affiliation: Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA. Electronic address: yipl@upmc.edu.
authors.forename: Linwah
authors.initials: L
authors.lastname: Yip
mesh_terms: D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D018570:Risk Assessment; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)