title: BRAFV600EMutation: Has It a Role in Cervical Lymph Node Metastasis of Papillary Thyroid Cancer?
abstract: BACKGROUND
  The BRAFV600Emutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear.
  
  
  OBJECTIVE
  Our aim was to evaluate the prevalence of the BRAFV600Emutation in primary tumors and accompanying LNM at the time of diagnosis.
  
  
  METHODS
  This retrospective study included 51 PTC patients (40 women, 11 men; mean age 40.0 ± 16.5 years; range 6-81) who underwent total thyroidectomy accompanied by a lateral neck dissection due to preoperatively detected LNM. Real-time PCR was used for the detection of the BRAFV600Emutation in specimens from primary thyroid tumors and metastatic lymph node tumors.
  
  
  RESULTS
  The prevalence of the BRAFV600Emutation was 64.7% (n = 33) in primary tumors and 47.1% (n = 24) in metastatic lymph nodes. Of 33 patients with BRAFV600E-positive primary tumors, 18 (54.5%) had BRAFV600E-positive metastatic lymph nodes. Of 18 patients with BRAFV600E-negative primary tumors, 6 (33.3%) had BRAFV600E-positive metastatic lymph nodes. The presence of the BRAFV600Emutation in the primary tumor did not affect the tumor size, but the diameter of metastatic lymph nodes significantly increased (by nearly 3 mm) with the presence of BRAFV600Ein LNM (p = 0.01).
  
  
  CONCLUSIONS
  In our study, the BRAFV600Emutation did not show a one-to-one correspondence. This indicates that the presence of BRAFV600Ein the primary tumor is not clonal and addresses the role of intratumor heterogeneity in PTC tumorigenesis. This supports the theses that mutations occur in the later stages of tumorigenesis, might be subclonal, and develop de novo, or that some other factors may be involved in the development of metastasis.
authors.affiliation: Endocrinology and Thyroid Clinic, Acibadem Maslak Hospital, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Kurtulmus
authors.affiliation: Otorhinolaryngology, Istanbul, Medical Faculty, Acibadem University, Istanbul, Turkey.
authors.forename: Burak
authors.initials: B
authors.lastname: Ertas
authors.affiliation: Pathology, Medical Faculty, Acibadem University, Istanbul, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Saglican
authors.affiliation: Endocrinology and Thyroid Clinic, Acibadem Maslak Hospital, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kaya
authors.affiliation: Pathology, Medical Faculty, Acibadem University, Istanbul, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Ince
authors.affiliation: Endocrinology and Thyroid Clinic, Acibadem Maslak Hospital, Istanbul, Turkey.
authors.forename: Mete
authors.initials: M
authors.lastname: Duren
keywords: BRAFV600E; Metastatic lymph node; Papillary thyroid cancer