Differentiated thyroid cancer is the most common malignant endocrine neoplasia, and its incidence continues to increase [1, 2]. In the United States (USA), 50,000 cases of PTC were reported in 2013(4), and it is currently the second most frequent malignancy diagnosed in Latinas in this country . In Colombia, the country with the second largest Latino population, the incidence of PTC has shown a similar trend; it is the third most common cancer in the country and affects 14.5 out of every 100,000 inhabitants. . Although it is considered a cancer with a good prognosis, 10% of patients follow an abnormal course, with aggressive biological behavior . It is therefore important to identify indicators of severity early.
The BRAF V600E mutation is specific for PTC and is associated with a worse prognosis [4, 17, 18]. The frequency of this mutation in the present study was 76.1% (16/21) of the cases. We previously reported a higher frequency in our population of individuals diagnosed with PTC who were older than 45 years. Frequencies of up to 90% are found in the literature worldwide [19, 20].
The BRAF V600E mutation has been controversially linked to different aggressive clinicopathological features [16, 19]. In a previous local study, we reported that this mutation is related to greater extrathyroid extension, lymphatic invasion, vascular invasion and lymph node involvement, but no relationship was found with respect to tumor size, multicentrality, bilaterality, Hashimoto's thyroiditis or the presence of metastasis . In the current patient sample, we were able to observe the presence of histological characteristics that have been associated with the BRAF mutation . In our group of patients, the presence of these histological variables showed sensitivity but was not highly specific. This technique could be translated into clinical practice as an option for an initial screening strategy, with mandatory molecular confirmation by PCR.
Most of the methods for BRAF V600E mutation detection are based on molecular tests and genomic sequencing, constituting the gold standard for detection. On the other hand, immunohistochemistry has emerged as a surrogate for these tests. In our case, the BRAF V600E mutation was detected by immunohistochemistry in 83.3% (15/18) of the cases. However, false negatives constituted 66.7% (2/3) of the cases, a nonnegligible percentage. This shows a high sensitivity with poor specificity, in our case less than histology. Limited studies report a lack of specificity for the detection of BRAF mutations by immunohistochemistry .
However, a better specificity of 82.2% has been obtained, much higher than that reported in our study . In both cases, the same antibody (clone VE-1) was used, which in the past was shown to detect BRAF V600E mutations in both PTC and melanomas, with a specificity and sensitivity of 100%, in adequately preserved samples ; however, different commercial kits were used.
In an 11-study meta-analysis that evaluated the concordance between immunohistochemical techniques and sequencing with real-time PCR, it was determined that the concordance rate was up to 92% among positive samples and 85.8% among negative samples for the BRAF V600E mutation by immunohistochemistry and by PCR. However, different types of cancer were included in the meta-analysis . In thyroid cancer, according to the limited literature, immunohistochemistry does not replace molecular analysis by PCR. Szymonek et al. confirmed this in their study, where the correlations did not exceed 76.2% . In this manner, our study confirms the low performance of immunohistochemistry in papillary thyroid cancer given its low specificity. However, it is necessary to consider certain limitations, such as the limited sample size and the possible inadequate conservation of the biological samples, as it is a retrospective study.