Is BRAF mutation associated with lymph node metastasis in patients with papillary thyroid cancer?

Lee, Kathleen C.; Li, Carol; Schneider, Eric B.; Wang, Yongchun; Somervell, Helina; Krafft, Matthew R.; Umbricht, Christopher B.; Zeiger, Martha A.

doi:10.1016/j.surg.2012.08.019

Cited by 46 publications

(27 citation statements)

References 24 publications

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“…These results support the hypothesis that the coexistence of CLT counteracts tumor progression and recurrence in PTC (Loh et al 1999, Kim et al 2009a, Lang et al 2014. Furthermore, there were previous studies that did not demonstrate the association between BRAF mutation and aggressive clinicopathological characteristics of PTC (Lee et al 2012a,b, Gouveia et al 2013, Kim et al 2015. These studies could explain why the impact of CLT was not different according to BRAF mutation status.…”

Section: Discussionsupporting

confidence: 81%

“…Numerous studies have demonstrated a strong association between the BRAF mutation and aggressive clinicopathological characteristics of PTC such as advanced stage, extrathyroidal extension (ETE), lymph node (LN) metastasis and tumor recurrence (Kebebew et al 2007, Lupi et al 2007, Xing 2007. However, there were other studies that did not demonstrate the association between the BRAF mutation and aggressive clinicopathological characteristics of PTC (Lee et al 2012a,b, Gouveia et al 2013, Kim et al 2015.…”

Section: Introductionmentioning

confidence: 99%

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Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

Kim¹,

Woo²,

Lee³

et al. 2015

Endocrine-Related Cancer

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It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (ORZ0.662, PZ0.023) and BRAF-positive (ORZ0.817, PZ0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (ORZ0.675, PZ0.044) and BRAF-positive (ORZ0.817, PZ0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status. Key Words" BRAF mutation " papillary thyroid carcinoma " chronic lymphocytic thyroiditis " central lymph node metastasis " extrathyroidal extension

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

Kim¹,

Woo²,

Lee³

et al. 2015

Endocrine-Related Cancer

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“…The most prevalent subgroup of classical and follicular variants of PTC showed no association of BRAF mutation with poor prognostic factors or poor outcome. Our findings corroborated recent studies (20,21,22,23) and also discarded the association of p.V600E with higher frequency of cervical LN and distant metastases (13,24,25,26). In order to justify the lack of association, it has also been proposed that it is not the intratumoral presence of BRAF mutation that determines prognosis but the higher frequency of mutant BRAF alleles, identified in an innovatory analysis of pyrosequencing technique, that favors more frequent recurrence (27).…”

Section: Clinical Study D L S Danilovic and Others Preoperative Molecsupporting

confidence: 90%

Pre-operative role of BRAF in the guidance of the surgical approach and prognosis of differentiated thyroid carcinoma

Danilovic

Lima

Domingues

et al. 2014

European Journal of Endocrinology

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Objective: The p.V600E BRAF and RAS mutations are found in 30-80% of differentiated thyroid carcinoma (DTC). BRAF mutation has been associated with poor prognosis. This study investigated the role of molecular studies in preoperative diagnosis of DTC and the association of p.V600E mutation with prognostic factors. Design: Prospective study. Methods: A total of 202 patients with cytological diagnosis of Bethesda III-VI underwent preoperative molecular studies and subsequent thyroidectomy. p.V600E and RAS mutations were studied in the cytology smears, using real-time PCR genotyping technique. The BRAF mutation (BRAF C or BRAF K ) was correlated with histological and clinical findings. Results: Molecular study of 172 nodules with Bethesda III-V cytology improved negative predictive value and accuracy of Bethesda III and IV diagnosis. BRAF mutation was present in 65% of 94 DTC and p.Q61R NRAS in one. Except for age, BRAF C and BRAF K did not differ in sex, tumor size, histological subtype, multifocality, vascular invasion, extrathyroidal extension, or prognostic staging. Among papillary carcinomas, lymph node (LN) metastasis was diagnosed in 23% BRAF C and 37% BRAF K . Distant metastasis occurred in four BRAF K . Recurrent or persistent disease was more frequent in BRAF K (26.7 vs 3.3% BRAF C , PZ0.002) along follow-up of 29.8G10 months. BRAF C patients without LN metastasis by pre-operative evaluation submitted to thyroidectomy with central neck dissection (CND) had more frequent LN metastasis (45 vs 5% no CND, PZ0.002), but no difference in clinical outcome was observed. Conclusions: Pre-operative identification of BRAF mutation improved cytological diagnosis of DTC, but it was not associated with poor prognostic factors. Prophylactic CND did not guarantee better outcome in BRAF C patients.

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“…The debate centers on whether the BRAF V600E mutation portends a higher risk of metastatic disease in the central compartment, and whether it should be used as a criterion for pCLND. Data are conflicting, because some studies have found BRAF V600E to be an independent predictor of central lymph node metastases [31], whereas others have not [32]. More data are likely needed here [33].…”

Section: Management Of Regional Lymph Nodesmentioning

confidence: 99%