The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors

The prognostic role of molecular markers in papillary thyroid carcinoma (PTC) is a matter of ongoing debate. The aim of our study is to investigate the impact of RAS, BRAF, TERT promoter mutations and RET/PTC rearrangements on the prognosis of PTC patients. We performed a search in four electronic databases: PubMed, Scopus, Web of Science and Virtual Health Library (VHL). Data of hazard ratio (HR) and its 95% confidence interval (CI) for disease-specific survival (DSS) and disease-free survival (DFS) were directly obtained from original papers or indirectly estimated from Kaplan–Meier curve (KMC). Pooled HRs were calculated using random-effect model weighted by inverse variance method. Publication bias was assessed by using Egger’s regression test and visual inspection of funnel plots. From 2630 studies, we finally included 35 studies with 17,732 patients for meta-analyses. TERT promoter mutation was significantly associated with unfavorable DSS (HR = 7.64; 95% CI = 4.00–14.61) and DFS (HR = 2.98; 95% CI = 2.27–3.92). BRAF mutations significantly increased the risk for recurrence (HR = 1.63; 95% CI = 1.27–2.10) but not for cancer mortality (HR = 1.41; 95% CI = 0.90–2.23). In subgroup analyses, BRAF mutation only showed its prognostic value in short-/medium-term follow-up. Data regarding RAS mutations and RET/PTC fusions were insufficient for meta-analyses. TERT promoter mutation can be used as an independent and reliable marker for risk stratification and predicting patient’s outcomes. The use of BRAF mutation to assess patient prognosis should be carefully considered.

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“…We received responses from authors of six studies in Korea, Italy, Poland and Turkey to provide their unpublished data (16, 17, 18, 19, 20, 21). …”

Section: Resultsmentioning

confidence: 99%

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma

Vuong

Duong

Altibi

et al. 2017

Endocrine Connections

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“…More than 80% of thyroid cancers are PTC, and the most common genetic alteration in PTC is BRAF V600E . Its frequency ranges from 30 to 80% of cases of PTC -in the Polish population it occurs in 68-70 % of PTC [9,12,13]. Because of the high prevalence of this mutation it was feasible to use BRAF mutation in FNAC as a marker of TC in our study.…”

Section: Discussionmentioning

confidence: 98%

Przydatność określania obecności mutacji BRAF V600E w biopsji aspiracyjnej celowanej cienkoigłowej w zmianach niezdeterminowanych

Kowalska

Kowalik

Pałyga

et al. 2016

Endokrynologia Polska

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Introduction: Fine-needle aspiration biopsy (FNAB) is regarded as the gold standard method for the diagnosis of thyroid nodules, but it has its limitations. Additional methods that would improve sensitivity and specificity in the diagnosis of thyroid cancer (TC), especially in indeterminate lesions. Molecular tests seem to be such a tool. BRAF V600E mutation (the most common in TC) can be detected in FNAB and can be potentially a very useful ancillary marker for FNAB practice. The aim of our study was to evaluate the usefulness of the detection of the BRAF V600E mutation in FNAC in the early diagnosis of TC in patients with indeterminate cytology. Material and method: 2290 FNAB were performed and 147 indeterminate results (group 3, 4, and 5 of the Bethesda system) were obtained. Material from these groups was submitted for molecular tests for the occurrence of BRAF V600E mutation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests were calculated. Results: Determining the presence of BRAF V600E mutation in FNAC material in groups 3 and 4 together and in group 5 is associated with sensitivity of TC diagnosis of 37.5% and 81.8%, respectively. In all cases the detection of BRAF V600E mutation was associated with histopathologically proving the presence of TC (specificity of the test -100%). Conclusions:1. The presence of BRAF V600E mutation in FNAC material is always associated with the presence of TC. 2. The usefulness of determining the presence of BRAF V600E in FNAC in cytological groups 3 and 4 is associated with low sensitivity in the diagnosis of thyroid cancer. 3. Due to its high specificity BRAF V600E study may be useful in determining the scope of surgery in patients in cytological group 5. (Endokrynol Pol 2016; 67 (1): 41-47)

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“…Since clinicopathological factors including LNM, advanced TNM stage, ETE, male gender and multifocality were reported to be crucial prognostic factors for PTC [98,99], BRAF mutation could be considered as a promising predictor of PTC prognosis. Moreover, BRAF mutation may provide additional assistance for tailoring the initial treatment and determining the appropriateness of radioactive iodine adjuvant treatment based on patients' clinical characteristics.…”

Section: Discussionmentioning

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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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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The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors

Cited by 35 publications

References 54 publications

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma

Przydatność określania obecności mutacji BRAF V600E w biopsji aspiracyjnej celowanej cienkoigłowej w zmianach niezdeterminowanych

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

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