The association between BRAF V600E mutation and pathological features in PTC

Liu, Xin; Yan, Kangkang; Lin, Xiaoqing; Zhao, Lanfei; An, Wenxiu; Wang, Chunpeng; Liu, Xiaodong

doi:10.1007/s00405-013-2872-7

Cited by 43 publications

(42 citation statements)

References 71 publications

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“…A similar meta-analysis [9] in 2014 suggested that BRAF mutation was associated with several factors including multifocality, ETE, LNM, TNM stage and recurrence. However, our meta-analysis incorporated more studies including seven studies conducted in 2015 and also examined how BRAF mutation is related to other factors such as gender, concomitant hashimoto thyroiditis, vascular invasion and tumor size.…”

Section: Discussionmentioning

confidence: 99%

“…As a member of RAF/RAS/MAPK/MAPK kinase signaling pathway, RAF genes have received special attention since this pathway is associated with the regulation of cell proliferation, growth and division [7,8]. BRAF is a cytoplasmic protein kinase and it is a main subtype of RAF kinase that could trigger tumorigenesis through the activation of MAPK pathway [9]. PTC patients with BRAF mutation are associated with higher risk of unfavorable clinicopathological characteristics [10].…”

Section: Introductionmentioning

confidence: 99%

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Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

Zhang

Liu²,

Guan³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I² were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF^V600E mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Results: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF^V600E mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF^V600E mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF^V600E mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). Conclusion: This meta-analysis confirmed significant associations between BRAF^V600E mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF^V600Emutation for PTC prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

Zhang

Liu²,

Guan³

et al. 2016

Cell Physiol Biochem

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“…The benefits of this approach are evident, for example, in undetermined cytology specimens in which the identification of a BRAF V600E mutation is almost 100% diagnostic of PTC. Similarly, TERT p mutation defines the diagnosis of malignancy in a thyroid nodule and also preoperatively identifies a TCDFC with higher aggressive potential, enabling better risk stratification [Liu X et al, 2014b]. Following the same reasoning, some authors suggest that a more accurate prediction of thyroid cancer outcome is possibly based on a more extensive genetic analysis, since, as discussed above, some data suggest a more aggressive clinical course in those patients harboring tumors with combination of other mutations such as TERT p and BRAF V600E or TERT p and RAS .…”

Section: Discussionmentioning

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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“…We have found similar frequency rates of TC types: PTC -89.62%, FTC -7.55%, MTC -1,89%, and ATC -0.94%. PTC is characterised by slow growth and long existence, thus patients generally have good 5-and 10-year survival rates [23,24]. The favourable survival is partly due to PTC being a normal finding; rather than being called carcinoma, some authors say it should be called a benign papillary tumour [25].…”

Section: Discussionmentioning

confidence: 99%

Wartość powtórnego badania stanu mutacji genu BRAF V600E w diagnostyce raka brodawkowatego tarczycy

Beiša

Stoškus

et al. 2016

Endokrynologia Polska

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Introduction: Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re-examining the BRAF V600E mutation in papillary thyroid carcinoma patients. Material and methods: All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. Results: Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. Conclusions: Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics.

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The association between BRAF V600E mutation and pathological features in PTC

Cited by 43 publications

References 71 publications

Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

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

Wartość powtórnego badania stanu mutacji genu BRAF V600E w diagnostyce raka brodawkowatego tarczycy

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