Clinical Significance of BRAF Mutation in Papillary Cancer

Abstract

Objective: BRAF mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency and its relationship with clinico-pathological parameters of poor outcome. We analyzed BRAF mutation in a cohort of patients affected by PTCs, to identify its association with clinical variables. Method: We analyzed retrospectively a series of 304 patients, treated for PTC from 1992 to 2011 at Bologna University Hospital. We searched BRAF mutation by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing, to correlate the presence of the mutation with clinico-pathological parameters of the patients. Results: BRAF mutation was found in 77.4% of classical PTCs, 31.9% of follicular variant, and 72.2% of high tall cell PTC, being significantly associated with recurrence ( P .005), stage ( P .043), and multicentricity ( P .025). Moreover BRAF was significantly associated with the classic variant of PTC ( P .0001). Higher T, but not N nor M stage, resulted to be associated to BRAF mutation. A significant difference of disease free survival time was found between BRAF mutation positive and BRAF mutation negative patients ( P .005) after a mean follow-up of 60.2 months (range 10-228). Conclusion: Our results indicate that BRAF mutation identifies a subset of PTC with increased risk of recurrence. The presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. In order to confirm the diagnostic usefulness of this marker, further studies should be carried out.