The present study showed an 85.4% frequency rate of the BRAFV600E mutation in conventional PTC, the proportion was slightly higher in the PTMC group. Previous studies have shown that the BRAFV600E mutation is common in PTC patients, the overall prevalence varying from 40.1% to 76.52% in Chinese patients with PTC [24-30] and from 33.2% to 70% in Western countries [11-23]. The possible reasons for the variation in positive mutation rates are PTC subtype, geographic region, ethnicity, and technical differences for BRAFV600E examination.
The present study showed that the BRAFV600E mutation was much more frequent in elderly patients in both the overall PTC group and PTC>10 mm group. Previous studies have also revealed an association between the BRAFV600E mutation and elderly patients [23, 27, 28]. The youngest patients in our cohort were 15 years of age. The positive rate of the BRAFV600E mutation was 60% (3/5) in patients <20 years of age, and it is interesting that this rate increased to more than 80% in those aged ≥20 years. The possible reason for this phenomenon is that the BRAFV600E mutation might occur early in thyroid carcinogenesis, in addition, the effect might become more remarkable along with the development and progress of PTC. However, no such relationship was noted in the results of other studies [24, 25, 29].
Furthermore, in the present study, the BRAFV600E mutation was more likely to be present in patients with a T1-stage tumor than in those with a T2- or T3-stage tumor in both overall and PTC >10 mm groups. This phenomenon also indicates that PTC patients having the BRAFV600E mutation might be susceptible to an early T stage, and that the mutation might play an important role in the early stages of PTC, but it might also slow PTC progression; however, no significant difference was found among TNM stages, perhaps because all patients enrolled in the present study were in the early stages of the cancer (0 and 1). Previous studies have also found no relationship between the BRAFV600E mutation and TNM stage [27-30].
Moreover, our data showed that the risk of having a large tumor was increased about 6-fold when BRAFV600E mutation in the PTMC group, however, no influence was found in the PTC>10 mm group. This occurrence also indicated that the BRAFV600E mutation might be an initiating factor in PTC; however, the probable effect decreased along withing. The reported studies have found no association between the mutation and tumor in PTMC [19, 29].
In addition, our results showed that the BRAFV600E mutation was more frequent in PTC patients without concomitant Hashimoto’s thyroiditis in both overall PTC and PTMC groups. The meta-analysis also suggested that patients negative for the BRAFV600E mutation were significantly more likely to have Hashimoto’s thyroiditis . Other previous studies found no association between BRAFV600E mutation and PTC concomitant Hashimoto’s thyroiditis [17-22]. The possible reason of such a discrepancy might be the result of the study population that was different between our study and the above-mentioned study.
There was no relationship between the BRAFV600E mutation and both lymph node metastasis and tumor stage in patients with PTC in the present study. Similar phenomena were also reported in previous studies [17-22, 30]; however, several studies have reported that the high-risk clinicopathologic parameters, such as lymph node metastasis and tumor stage, were associated with the BRAFV600E mutation [10-16, 25-29]. The inconsistent results might be because of the following factors: geography or ethnicity, sample size, tumor subtypes, or the method used to test the BRAFV600E mutation. In addition, 88.5% of patients with PTC (838/947) enrolled in the present study were at early stages of the disease, limiting the effect of the BRAFV600E mutation on progressive clinical characteristics.
The results of our study found no association between the BRAFV600E mutation and disease-free survival. Similar results were found in studies on both Korean and Japanese populations [10, 13, 20]; however, the BRAFV600E mutation was reported as an independent prognostic factor in patients with PTC [19, 24]. Numerous reports have indicated that the BRAFV600E mutation is associated with disease-free survival even in patients in the early stages of the disease [25-28]. The discrepancy among the results of the published studies might be associated with sample size, geographic and ethnic differences, duration of follow-up, and treatment regimen. Most patients with PTC are diagnosed at early stages of the disease and have a low mortality rate. Majority of the patients enrolled in the present study were at T1 or T2 stage at the time of diagnosis. The intensive initial treatment might be a potential reason for finding no association between the BRAFV600E mutation and the disease because patients received all scheduled treatments [13, 30].
Strengths of the present study. Firstly, we analyzed the relationship between BRAFV600E mutation and clinicopathological features in both PTMC and PTC> 10mm groups and found that there were different features in each group. Secondly, subjects enrolled in the present study were only conventional PTC to exclude heterogeneity and variations in tumor subtypes. Limitation of our study. Majority of patients enrolled in the present study were at T1or T2 stage when diagnosis and the limited time of follow-up were constrict the effect of clarifying the relationship of BRAFV600E mutation and prognosis.