The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma

Clin Endocrinol (Oxf). 2006 Sep;65(3):364-8. doi: 10.1111/j.1365-2265.2006.02605.x.

Abstract

Background: The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue.

Aim: To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC.

Patients and methods: The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing.

Results: The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis.

Conclusions: Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / surgery
  • Female
  • Fluorodeoxyglucose F18
  • Follow-Up Studies
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Point Mutation*
  • Positron-Emission Tomography
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics*
  • Radiopharmaceuticals / therapeutic use
  • Survival Analysis
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / surgery
  • Thyroidectomy

Substances

  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf