Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto's thyroiditis

Abstract

The purpose of the present study was to investigate the frequency of BRAF mutations in human papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) and to evaluate the association of the BRAF mutation with the clinicopathological features of both of these thyroid disorders. A total of 51 PTC with no HT, 28 PTC with HT and 27 HT with no PTC were evaluated using DNA extracted from paraffin-embedded specimens. BRAF mutations were analyzed by direct DNA sequencing of the polymerase chain reaction (PCR)-amplified exon 15. The BRAF missense mutation at codon 599 (T1796A) was present in 46 of 51 PTC (90%) with no HT, 18 of 28 PTC (64%) with HT, four of 28 HT (14%) with PTC, and zero of 27 HT with no PTC. The BRAF mutation at codon 600 (A1798G) was not detected in any case. Clinicopathological examination of 106 patients with either PTC or HT showed that the BRAF mutation was significantly correlated with patient age. These data indicate that the BRAF mutation is associated with a valuable biological property of PTC and may participate in the pathogenesis of PTC arising in HT. These results indicate that the detection of the BRAF mutation in HT can be helpful for prediction of progress to PTC.

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

“…In this study, we performed a multivariate analysis and revealed that CLT was an independent predictor for the low prevalence of (Monaco 2012), and we consistently found a strong association of CLT with female gender, regardless of BRAF mutation status. It has been suggested that concurrent CLT is significantly associated with a lower frequency of BRAF mutations (Kim et al 2005a, Kim et al 2009b), and we also observed that the BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%, P!0.001). A recent study proposed that the prevalence of the BRAF mutation in patients with CLT has been underestimated by a dilution effect on the mutated alleles of infiltrating lymphocytes, which carry WT BRAF (Guerra et al 2012).…”

“…On the other hand, some investigators have reported that PTC with the coexistence of CLT is less associated with ETE, advanced stage, LN metastasis and recurrence (Loh et al 1999, Kim et al 2009a, Lang et al 2014. Interestingly, in two previous studies focused on BRAF mutation status in patients with PTC with and without CLT in a Korean population, the BRAF mutation was found less frequently in subjects with CLT than without CLT (64% vs 90% and 72.9% vs 95.3% respectively) (Kim et al 2005a, Kim et al 2009b. Moreover, there was a study that suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients (Marotta et al 2013).…”

Carcinoma papilífero da tireoide associado à tireoidite de Hashimoto: frequência e aspectos histopatológicos

“…No entanto, os dados são incompletos e conflitantes em algumas áreas, como, por exemplo, quanto às mutações BRAF. Um estudo para investigar essa hipótese (12) mostrou que cerca de 14% dos casos de tireoidite abrigavam as mutações BRAF, diferindo do estudo (15) que relatou resultados negativos.…”

Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma

“…15 In Korea, BRAF V600E mutation has been detected at a greater frequency in papillary thyroid carcinoma without concurrent Hashimoto thyroiditis than in papillary thyroid carcinoma with Hashimoto thyroiditis. 20,21 In this study, the mutation was found in 10 (56%) of 18 patients with background Hashimoto thyroiditis, but in 152 (79%) of 192 patients without Hashimoto thyroiditis (Table 3). To establish the correlation between Hashimoto thyroiditis, papillary thyroid carcinoma and BRAF V600E mutation, it is necessary to study as many cases of coexistent Hashimoto thyroiditis with papillary thyroid carcinoma as possible.…”