BRAF^V600E Mutation: Has It a Role in Cervical Lymph Node Metastasis of Papillary Thyroid Cancer?

Abstract

Background: The BRAF^V600E mutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear. Objectives: Our aim was to evaluate the prevalence of the BRAF^V600E mutation in primary tumors and accompanying LNM at the time of diagnosis. Methods: This retrospective study included 51 PTC patients (40 women, 11 men; mean age 40.0 ± 16.5 years; range 6-81) who underwent total thyroidectomy accompanied by a lateral neck dissection due to preoperatively detected LNM. Real-time PCR was used for the detection of the BRAF^V600E mutation in specimens from primary thyroid tumors and metastatic lymph node tumors. Results: The prevalence of the BRAF^V600E mutation was 64.7% (n = 33) in primary tumors and 47.1% (n = 24) in metastatic lymph nodes. Of 33 patients with BRAF^V600E-positive primary tumors, 18 (54.5%) had BRAF^V600E-positive metastatic lymph nodes. Of 18 patients with BRAF^V600E-negative primary tumors, 6 (33.3%) had BRAF^V600E-positive metastatic lymph nodes. The presence of the BRAF^V600E mutation in the primary tumor did not affect the tumor size, but the diameter of metastatic lymph nodes significantly increased (by nearly 3 mm) with the presence of BRAF^V600E in LNM (p = 0.01). Conclusions: In our study, the BRAF^V600E mutation did not show a one-to-one correspondence. This indicates that the presence of BRAF^V600E in the primary tumor is not clonal and addresses the role of intratumor heterogeneity in PTC tumorigenesis. This supports the theses that mutations occur in the later stages of tumorigenesis, might be subclonal, and develop de novo, or that some other factors may be involved in the development of metastasis.

Fine Needle Biopsy Versus Core Needle Biopsy Combined With/Without Thyroglobulin or BRAF 600E Mutation Assessment for Detecting Cervical Nodal Metastasis of Papillary Thyroid Carcinoma

“…No researchers have yet analyzed the association between cervical LNM and CNB-T in thyroid cancer, so it remains unclear whether CNB-T is superior to FNAB-C in indicating LNM. In addition, the BRAF V600E mutation is the most common genetic alteration in thyroid cancer and occurs in nearly 80% of primary tumors and 50% of metastatic lymph nodes (22,23). It therefore remains unknown whether the introduction of BRAF V600E mutation assessment could increase the diagnostic reliability of CNB-T and FNAB-C.…”

Molecular Heterogeneity of Papillary Thyroid Cancer: Comparison of Primary Tumors and Synchronous Metastases in Regional Lymph Nodes by Mass Spectrometry Imaging

“…tumor and mutation-positive metastases were also frequently reported [13,14,34,35]. An interesting genomics study was reported by Le Pennec et al [15] who performed a systemic cDNA sequencing screening of a primary tumor (different subregions), lymph node metastases and distant (pleural) metastasis in a patient with an aggressive PTC.…”

BRAF V600E and lymph node metastases in papillary thyroid cancer

“…Indeed, when the size of the largest metastatic focus of LNM was ≥0.65 cm, the BRAF V600E mutation frequency was lower. In contrast, Kurtulmus et al showed that BRAF V600E-positive metastatic lymph nodes were greater in diameter than those without the BRAF V600E mutation ( 10 ). Different results may be due to the remarkably lower overall BRAF V600E positivity in LNM in their study (47.1%, 24/51) compared with our study (78.0%, 291/373) and other studies (73.9, 81.0%) ( 21 , 22 ).…”

“…Moreover, some scientists hope that we may extend our observation to metastatic PTC to generate a critical mass of data for clinical practice ( 8 ). However, only a few studies have examined BRAF V600E mutation in metastases, such as lymph node metastasis (LNM) ( 9 , 10 ). The PTC prognosis is usually favorable with appropriate treatment, however, LNM can develop during early stages of the disease ( 11 ).…”