scholarly journals The ratio of BRAFV600E alleles can be used to assess the biological behavior of papillary thyroid carcinoma

Author(s):  
Dingcun Luo ◽  
Yeqin Ni ◽  
Shirong Zhang ◽  
Yanping Xun ◽  
Pan Zhao ◽  
...  

ABSTRACTBackgroundThe BRAFV600E mutations is an important molecular event in the occurrence and development of papillary thyroid carcinoma (PTC). A qualitative detection of the BRAFV600E mutation is still insufficient to explain the biological behavior of PTC. Though quantitative detection of the BRAFV600E mutation can reflect certain characteristics of PTC, its clinical value is still controversial. We aimed to investigate the association between the ratio of BRAFV600E alleles and clinicopathological parameters in PTC patients.MethodsGenomic DNA was extracted from specimens obtained from 329 PTC patients undergoing thyroidectomy. The ratio of BRAFV600E alleles was determined by amplification refractory mutation system (ARMS) and droplet digital polymerase chain reaction (ddPCR). Inconsistent results were further verified by next-generation sequencing (NGS). The clinicopathologic features, clinical tumor stage, and tumor recurrence risk stratification of all patients were correlated with the ratio of BRAFV600E alleles.ResultsThe sensitivity of ddPCR was superior to that of ARMS and almost the same as that of NGS. In total, 275 of 329 patients had the BRAFV600E mutation as determined by ARMS, ddPCR and NGS. The ratio of BRAFV600E alleles ranged from 0.17%-48.0%, with a median ratio of 12.58%, and significantly correlated with tumor size (p<0.001), capsule or extrathyroidal invasion (p<0.001), the number or rate of lymph node metastases (p<0.001), tumor stage (p=0.006) and tumor recurrence risk (p<0.001) but not with sex, age or multifocality. The ratio of BRAFV600E alleles was much lower in PTC patients with Hashimoto’s thyroiditis than in those without (p<0.001).ConclusionsThe ratio of BRAFV600E alleles can reliably reflect the biological behavior of PTC, making it a molecular-based stratification index of recurrence risk. The quantitative detection of BRAFV600E has the potential to guide the clinical diagnosis and treatment of PTC.

Apmis ◽  
2016 ◽  
Vol 124 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Aleksandar Bartolome ◽  
Srdjan Boskovic ◽  
Ivan Paunovic ◽  
Vesna Bozic ◽  
Dubravka Cvejic

2020 ◽  
Vol 72 (1) ◽  
pp. 37-44
Author(s):  
Ivan Paunovic ◽  
Sonja Selemetjev ◽  
Tijana Isic-Dencic ◽  
Ilona Djoric ◽  
Jelena Jankovic-Miljus ◽  
...  

Papillary thyroid carcinoma (PTC) generally has a good prognosis, but in a subset of patients it progresses to aggressive forms. Analysis of molecular alterations in relation to clinical phenotype may help in risk stratification of patients by predicting tumor aggressiveness. We analyzed the expression profiles of epidermal growth factor receptor (EGFR) using immunohistochemistry and the presence of BRAF(V600E) mutation by mutant allele-specific PCR in PTC tissue samples (n=92) in relation to clinicopathological parameters. BRAFV600E was detected in 46.7% of patients and correlated with the presence of lymph node metastasis (LNM, p=0.035) and extrathyroid invasion (EI, p<0.0001). EGFR overexpression was detected in 52.2% of the patients and also correlated with LNM (p<0.0001) and EI (p=0.027). Among patients with a single alteration, the presence of BRAFV600E impacted EI, while EGFR overexpression alone had a greater impact on LNM. The strongest association with adverse features was found in PTC patients with coexisting BRAFV600E and EGFR overexpression (28.3%), among whom LNM and EI were evident in 73% and 69%, respectively (p<0.0001, for both). Thus, the coexistence of BRAFV600E mutation and EGFR overexpression identifies high-risk PTC patients, who should be considered for combined molecular therapy offering a better long-term therapeutic outcome.


2014 ◽  
Vol 2 (4) ◽  
Author(s):  
Emine Demirbaş ◽  
Mehmet Aşık ◽  
Semra Özdemir ◽  
Hacer Şen ◽  
Fahri Güneş ◽  
...  

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.


2018 ◽  
Vol 25 (6) ◽  
pp. 1775-1781 ◽  
Author(s):  
Jong-kyu Kim ◽  
Chan Yong Seong ◽  
In Eui Bae ◽  
Jin Wook Yi ◽  
Hyeong Won Yu ◽  
...  

2009 ◽  
Vol 9 (19) ◽  
pp. 3593-3597 ◽  
Author(s):  
J. Mohammadi- ◽  
B. Larijani ◽  
Z. Khorgami ◽  
S.M. Tavangar ◽  
V. Haghpanah ◽  
...  

2019 ◽  
Vol 26 (2) ◽  
pp. 129-135 ◽  
Author(s):  
Oksana Sulaieva ◽  
Olena Chernenko ◽  
Yelisaveta Chereshneva ◽  
Dibahan Tsomartova ◽  
Oleksandr Larin

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