The relationship between the BRAFV600E mutation in papillary thyroid microcarcinoma and clinicopathologic factors

Choi, Sun Yi; Park, Heon-Soo; Kang, Myung Koo; Lee, Dong Kun; Lee, Kang Dae; Lee, Hyoung Shin; Kim, Sung Won; Lee, Eun Nam; Hong, Jong Chul

doi:10.1186/1477-7819-11-291

Cited by 48 publications

(55 citation statements)

References 12 publications

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“…To date, many studies suggested that Hashimoto's thyroiditis was associated with higher frequency of wild-type BRAF. 12,[23][24][25] In this study, DLI with positive TPOAb was a negative independent factor of BRAF V600E mutation and extrathyroidal extension in PTC but DLI without TPOAb was not. [5][6][7][8] However, there were also many studies that reported the BRAF status was not associated with Hashimoto's thyroiditis, or BRAF V600E mutation was even more frequently observed when Hashimoto's thyroiditis was present.…”

Section: Discussionmentioning

confidence: 46%

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Lee

Park

et al. 2018

Head & Neck

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Section: Discussionmentioning

confidence: 46%

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Lee

Park

et al. 2018

Head & Neck

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“…In contrast, BRAFV600E may have relatively limited prognostic utility in areas, such as Korea, where the BRAFV600E mutation has an extremely high prevalence (Jung et al . 2010, Choi et al . 2013, Chung et al .…”

Section: Discussionmentioning

confidence: 99%

BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis

Li¹,

Chen²,

Sheng³

et al. 2015

Endocrine-Related Cancer

114

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The prognostic value of the BRAFV600E mutation, resulting in poor clinical outcomes of papillary thyroid carcinoma, has been generally confirmed. However, the association of BRAFV600E with aggressive clinical behaviors of papillary thyroid microcarcinoma (PTMC) has not been firmly established in individual studies. We performed this meta-analysis to examine the relationship between BRAFV600E mutation and the clinicopathological features of PTMC. We conducted a systematic search in PubMed, EMBASE, and the Cochrane library for relevant studies. We selected all the studies that reported clinicopathological features of PTMC patients with information available on BRAFV600E mutation status. Nineteen studies involving a total of 3437 patients met these selection criteria and were included in the analyses. The average prevalence of the BRAFV600E mutation was 47.48%, with no significant difference with respect to patient sex (male versus female) and age (younger than 45 years versus 45 years or older). Compared with the WT BRAF gene, the BRAFV600E mutation was associated with tumor multifocality (odds ratio (OR) 1.38; 95% CI, 1.04–1.82), extrathyroidal extension (OR 3.09; 95% CI, 2.24–4.26), lymph node metastases (OR 2.43; 95% CI, 1.28–4.60), and advanced stage (OR 2.39; 95% CI, 1.38–4.15) of PTMC. Thus, our findings from this large meta-analysis definitively demonstrate that BRAFV600E-mutation-positive PTMC are more likely to manifest with aggressive clinicopathological characteristics. In appropriate clinical settings, testing for the BRAFV600E mutation is likely to be useful in assisting the risk stratification and management of PTMC.

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“…Recurrence is the most commonly described clinical and pathological feature associated with this mutation [Xing, 2010;Sancisi et al, 2012;Melo et al, 2015;Tavares et al, 2016]. In the majority of the series displaying associations between the BRAF V600E mutation and diseasespecific mortality, the association, when present, is dependent on underlying clinical and pathological features [Fugazzola et al, 2006;Xing, 2007;Ito et al, 2009;Kwak et al, 2009;Lee et al, 2009;Handkiewicz-Junak et al, 2010;Kim TH et al, 2012;Kurtulmus et al, 2012;RicarteFilho et al, 2012;Sarne, 2012;Tufano et al, 2012;Choi et al, 2013;Xing et al, 2013Xing et al, , 2014Xing et al, , 2015George et al, 2015;Melo et al, 2015;Shi et al, 2015]. Henke et al [2015] corroborated these findings in a study involving 508 patients with PCT where the BRAF mutation was present in 67% of the cases.…”

Section: Braf Mutations In Tcdfcmentioning

confidence: 99%

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes

Penna

Vaisman

et al. 2016

Cytogenet Genome Res

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Thyroid cancer derived from follicular cells (TCDFC) comprises well-differentiated (papillary and follicular) carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma. Papillary thyroid carcinoma is the most common endocrine cancer, and its incidence is steadily increasing. Lethality and aggressiveness of TCDFC is inversely correlated with differentiation degree. In this review, an emphasis has been put on molecular markers involved in tumorigenesis of thyroid carcinoma with a focus on aggressive histotypes and the role of such biomarkers in predicting thyroid cancer outcome. Genetic rearrangements in TCDFC (RET/PTC, PAX8/PPARG) and mutations in RAS, BRAF, TERT promoter (TERTp), TP53, PIK3CA, and AKT1 are discussed. The majority of the studies to date indicate that TERTp mutations can serve as a marker of more aggressive disease in all the subtypes of thyroid carcinoma, being the best current marker of poor prognosis, due to its independent association with distant metastases and increased disease-specific mortality. Some studies suggested that a more accurate prediction of thyroid cancer outcome may be possible through a more extensive genetic analysis. The same is true concerning the identification of other mutations that are only relatively frequent in advanced tumors (e.g., TP53, PIK3CA, or AKT1). A better understanding of the prognostic role of TERTp mutation (together with additional ones like BRAF, RAS, PIK3CA, AKT1, or TP53) and the clarification of their putative role in fine-needle aspiration biopsies are likely to allow, in the future, an early refinement of the stratification risk in patients with well-differentiated carcinomas. It is worth noting that, as with any categorical staging system, the risk evaluation within each category (low, intermediate, and high) varies depending on the specific clinicopathologic features of individual patients and the specific biological behavior of the tumor. Finally, besides the diagnostic and/or prognostic significance of the above-mentioned mutations, it is crucial to understand that the molecular pathways and epigenetic alterations will likely turn into interesting targets for new therapies.

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The relationship between the BRAFV600E mutation in papillary thyroid microcarcinoma and clinicopathologic factors

Cited by 48 publications

References 12 publications

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes

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The relationship between the BRAFV600E mutation in papillary thyroid microcarcinoma and clinicopathologic factors

Cited by 48 publications

References 12 publications

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation

BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes

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Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation