American Association of Endocrine Surgeon| Volume 148, ISSUE 6, P1139-1146, December 2010

BRAFV600E mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer


      The role of the B-isoform of the Raf kinase (BRAF) mutation BRAFV600E as an independent prognostic factor in papillary thyroid cancer (PTC) remains controversial. Some studies suggest that tumors containing BRAFV600E have decreased radioiodine avidity and present a greater risk of nodal recurrence and distant metastases.


      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 BRAFV600E mutation was determined by restriction digest. Tumor characteristics and long-term disease outcomes were analyzed according to BRAFV600E status.


      BRAFV600E 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 BRAFV600E-positive patients, and all patients required lateral neck dissection (P = .02). In contrast, subclinical nodal recurrence occurred in 7% of BRAFV600E-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 BRAFV600E mutation (P = .08). All 5 disease-related deaths occurred in patients with BRAFV600E-positive primary tumors (P = .06).


      The BRAFV600E mutation in PTC is associated with an increased risk of palpable nodal recurrence and the need for reoperative surgery.
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