The BRAF V600E Mutation Influences the Short- and Medium-Term Outcomes of Classic Papillary Thyroid Cancer,But Is Not an Independent Predictor of Unfavorable Outcome

Abstract

Introduction:

The prognostic usefulness of BRAF^V600E evaluation in papillary thyroid cancer (PTC) has been analyzed in many studies, with controversial conclusions.

Aim:

To analyze the clinical relevance of BRAF^V600E measurement in a homogenous series of PTC patients followed in a single institution.

Methods:

One hundred three classical variant PTC patients who underwent total thyroidectomy in the 3-year period between 2005 and 2008 were retrospectively selected, and BRAF^V600E assessment was performed using paraffin-embedded archival specimens in 2013. All patients were actively followed at our medical center, with an average follow-up of 55±13 months.

Results:

BRAF^V600E mutation-positive cancers (55.3%) were more frequently associated with lymph node metastasis (p=0.01) and advanced TNM stage (III–IV) (p=0.03). These findings were also confirmed in the subset of 42 microcarcinomas. BRAF^V600E -positive patients were also at a higher risk of persistent disease (OR 3.5 [95% confidence interval {CI} 1.2–10.3], p=0.03) in univariate but not multivariate analysis (OR 2.8 [CI 0.7–11.8], p=0.2). Lymph node involvement was an independent predictor of persistent disease (OR 30.9 [CI 6.0–159.0], p<0.0001). Kaplan-Meier curves confirmed a higher percentage of persistent/recurrent disease in BRAF^V600E -positive patients (p=0.02). However, the BRAF^V600E mutation did not change the recurrence rate of PTC in subgroup analyses on the basis of other established risk factors (p=0.2).

Conclusions:

BRAF^V600E -positive tumors were at higher risk of developing more aggressive behavior and were associated with less favorable outcomes in the short and medium term, but the BRAF^V600E mutation was not an independent predictor of unfavorable outcome. Therefore, its use as a prognostic marker in clinical practice is not advisable.