Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma

Ann Surg. 2006 Nov;244(5):799-804. doi: 10.1097/01.sla.0000224751.80858.13.


Objective: To define the role of BRAF gene mutation in the progression of papillary thyroid carcinoma.

Summary background data: BRAF gene mutation is frequently detected in papillary thyroid carcinoma. Its role in pathogenesis or progression is under investigation.

Methods: Patients who underwent thyroidectomy and sentinel lymph node biopsy for papillary thyroid cancer were accrued. BRAF mutation was assessed in primary tumors and matched sentinel lymph nodes by a quantitative real-time PCR assay.

Results: Tissue specimens from 103 consecutive patients were evaluated. BRAF mutation of the primary tumor was detected in 34 (33%) patients. In 26 of 34 (76%) patients with BRAF mutation, concomitant lymph node metastasis was detected. On the contrary, in 69 patients with BRAF mutation-negative primary tumors, only 12 (17%) patients had lymph node metastasis (chi, P < 0.0001). BRAF mutation was detected in 20 of 26 (77%) lymph node metastases matched to BRAF mutation-positive primary tumors; it was not detected in lymph node metastases matched to BRAF mutation-negative primary tumors. Univariate analysis identified age, stage, tumor size, and BRAF mutation as prognostic factors for lymph node metastasis. In multivariate analysis, only BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5-34.0, P < 0.0001).

Conclusions: BRAF mutation may be a key genetic factor for the metastatic progression of papillary thyroid carcinoma. The study demonstrates that this gene mutation is a significant risk factor for locoregional lymph node metastasis and has potential utility as a surrogate marker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / secondary
  • Child
  • DNA, Neoplasm / genetics*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sentinel Lymph Node Biopsy
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • DNA, Neoplasm
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf