title: The role of molecular markers and tumor histological type in central lymph node metastasis of papillary thyroid carcinoma.
abstract: OBJECTIVE
  To look for genetic mutations that might predict central compartment lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) using strict criteria for N0 and N1 disease.
  
  
  METHODS
  We identified patients with PTC from our institution's pathology archives. Strict criteria were used for assessing the presence or the absence of central neck LNM. Disease was classified as N0 only if a comprehensive ipsilateral and pretracheal central neck dissection was performed and if pathological analysis revealed no evidence of LNM. Primary tumor samples were analyzed for a panel of known or suspected PTC-associated molecular markers, including BRAF, RET -PTC, KRAS, NRAS, HRAS, PIK3CA, and their variants.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Three hundred eighty-nine patients with PTC.
  
  
  METHODS
  Molecular mutations in tumors with and without LNM.
  
  
  RESULTS
  Of 389 identified cases, 209 fit the inclusion criteria, with 158 classified as node positive (N1) and 51 as node negative (N0). The follicular variant histological type was present in 7 of 158 N1 tumors (4.4%) and 24 of 51 N0 tumors (47.1%) and thus was strongly associated with lack of central neck metastasis in this study (odds ratio, 0.05; 95% CI, 0.02-0.14). Predictive factors for central LNM included extracapsular extension, angiolymphatic invasion, and higher T stage (T3 and T4). The BRAF mutation was more prevalent in the classic PTC histological type than the follicular variant. None of the molecular marker mutations that were analyzed in this study, including the BRAF mutation, predicted LNM in classic PTC.
  
  
  CONCLUSIONS
  Positive risk factors for central LNM include male sex, extracapsular extension, angiolymphatic invasion, and advanced T stage. The follicular variant histological type has a significantly lower incidence of central neck metastasis. In contrast to recent studies, the BRAF mutation was not significantly associated with central neck LNM from PTC when using a strict definition of a central neck dissection.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, 97239, USA.
authors.forename: Lorien
authors.initials: L
authors.lastname: Paulson
authors.forename: Maisie
authors.initials: M
authors.lastname: Shindo
authors.forename: Kathryn
authors.initials: K
authors.lastname: Schuff
authors.forename: Christopher
authors.initials: C
authors.lastname: Corless
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D037981:Neck Dissection; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D005819:Genetic Markers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf