Clinical implications of the extent of BRAF V600E alleles in patients with papillary thyroid carcinoma.

OBJECTIVE: There are many conflicting reports about the clinical implications of BRAFV600E in papillary thyroid cancer (PTC). We investigated the associations between the extent of BRAFV600E alleles and both clinico-pathological features and recurrence of PTC.

MATERIALS AND METHODS: Carcinoma tissues from 60 patients with PTC were genotyped for BRAFV600E using pyrosequencing, and the clinico-pathological factors and disease outcomes of the patients were examined. The associations between the extent of mutant BRAF alleles and both clinico-pathological parameters and recurrence-free survival (RFS) were analyzed.

RESULTS: The BRAFV600E mutation was detected in 66.7% (40/60) of our PTC patients. When we defined four groups on the basis of the extent of BRAFV600E alleles by pyrosequencing-negative (less than 5%), low (5 - less than 15%), intermediate (15 - less than 25%), and high (25% or greater)- the four groups showed statistically significant differences regarding lymph node (LN) metastasis and recurrence (P<0.05). However, age, gender, tumor size, multicentricity, capsular invasion, and lymphovascular invasion were not significantly different among the groups. The 10-year RFS rates in PTC patients with greater than 25% and less than 25% mutated BRAF alleles were 74% and 100%, respectively. This difference was significant (P=0.043).

CONCLUSIONS: A high extent more than 25% of BRAFV600E alleles may be associated with disease outcome in PTC patients. We need more data to verify a hypothesis that the extent of BRAF mutations may be clinically informative in the management of PTC, such as by tailoring proper surgical and radioactive iodine treatments and determining appropriate management during follow-up.