BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer

Surgery. 2010 Dec;148(6):1139-45; discussion 1145-6. doi: 10.1016/j.surg.2010.09.005.

Abstract

Background: The role of the B-isoform of the Raf kinase (BRAF) mutation BRAF(V600E) as an independent prognostic factor in papillary thyroid cancer (PTC) remains controversial. Some studies suggest that tumors containing BRAF(V600E) have decreased radioiodine avidity and present a greater risk of nodal recurrence and distant metastases.

Methods: Paraffin-embedded specimens from consecutive patients who underwent surgery for PTC before 2003 were independently reviewed by an endocrine pathologist. DNA was extracted, amplified by polymerase chain reaction, and the presence of the BRAF(V600E) mutation was determined by restriction digest. Tumor characteristics and long-term disease outcomes were analyzed according to BRAF(V600E) status.

Results: BRAF(V600E) was identified in 60 (59%) of 101 patients. At a median follow-up of 106 months, the overall disease-free survival was 78%. Clinically evident nodal recurrence occurred in 11% of BRAF(V600E)-positive patients, and all patients required lateral neck dissection (P = .02). In contrast, subclinical nodal recurrence occurred in 7% of BRAF(V600E)-negative patients, and all recurrences were successfully ablated with radioactive iodine. There was a trend toward poorer disease-free survival among patients with stage III/IV PTC and BRAF(V600E) mutation (P = .08). All 5 disease-related deaths occurred in patients with BRAF(V600E)-positive primary tumors (P = .06).

Conclusion: The BRAF(V600E) mutation in PTC is associated with an increased risk of palpable nodal recurrence and the need for reoperative surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma
  • Carcinoma, Papillary
  • DNA Primers
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / surgery*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Reoperation / statistics & numerical data*
  • Restriction Mapping
  • Risk Factors
  • Sex Characteristics
  • Survival Rate
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery

Substances

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