scholarly journals Coexistence of BRAFV600E mutation and EGFR overexpression is highly associated with adverse clinicopathological features of papillary thyroid carcinoma

2020 ◽  
Vol 72 (1) ◽  
pp. 37-44
Author(s):  
Ivan Paunovic ◽  
Sonja Selemetjev ◽  
Tijana Isic-Dencic ◽  
Ilona Djoric ◽  
Jelena Jankovic-Miljus ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Expression Profiles ◽  
Growth Factor Receptor ◽  
Molecular Therapy ◽  
Braf V600e ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Tissue Samples

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.

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

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.

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

2020 ◽  
Author(s):  
Dingcun Luo ◽  
Yeqin Ni ◽  
Shirong Zhang ◽  
Yanping Xun ◽  
Pan Zhao ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Tumor Recurrence ◽  
Recurrence Risk ◽  
Tumor Stage ◽  
Biological Behavior ◽  
Clinicopathological Parameters ◽  
Quantitative Detection ◽  
Papillary Thyroid ◽  
Brafv600e Mutation

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.

scholarly journals Papillary Thyroid Carcinoma Tissue miR-146b, -21, -221, -222, -181b Expression in Relation with Clinicopathological Features

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 418
Author(s):  
Aistė Kondrotienė ◽  
Albertas Daukša ◽  
Daina Pamedytytė ◽  
Mintautė Kazokaitė ◽  
Aurelija Žvirblienė ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Univariate Analysis ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Node Metastases

We analyzed miR-146b, miR-21, miR-221, miR-21, and miR-181b in formalin fixed paraffin-embedded papillary thyroid carcinoma (PTC) tissue samples of 312 individuals and evaluated their expression relationship with clinicopathological parameters. A higher expression of miR-21 was related to unifocal lesions (p < 0.011) and autoimmune thyroiditis (0.007). miR-221, miR-222 expression was higher in the PTC tissue samples with extrathyroidal extension (p = 0.049, 0.003, respectively). In a group of PTC patients with pT1a and pT1b sized tumors, the expression of miR-146b, miR-21, miR-221, and miR-222 in PTC tissue samples was lower than in patients with pT2, pT3, and pT4 (p = 0.032; 0.0044; 0.003; 0.001; 0.001, respectively). Patients with lymph node metastases had higher expression of miR-21, -221, -222, and -181b (p < 0.05). A high expression of miR-146b, miR-21, miR-221 panel was associated with decreased overall survival (OS) (Log rank p = 0.019). Univariate analysis revealed that presence of metastatic lymph nodes and high expression of miR-146b, miR-21, and miR-221 panels were associated with increased hazard of shorter OS. After multivariate analysis, only sex (male) and age (≥55 years) emerged as independent prognostic factors associated with shorter OS (HR 0.28 (95% CI 0.09–0.86) and HR 0.05 (95% CI 0.01–0.22), respectively). In conclusion, 5 analyzed miRs expression have significant relations to clinicopathologic parameters so further investigations of these molecules are expedient while searching for prognostic PTC biomarkers.

scholarly journals Association of BRAF V600E Mutation with Poor Clinicopathological Outcomes in 500 Consecutive Cases of Papillary Thyroid Carcinoma

2007 ◽  
Vol 92 (11) ◽  
pp. 4085-4090 ◽  
Author(s):  
Cristiana Lupi ◽  
Riccardo Giannini ◽  
Clara Ugolini ◽  
Agnese Proietti ◽  
Piero Berti ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf Mutation ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Braf Mutations ◽  
Tumor Capsule ◽  
Extrathyroidal Invasion

Abstract Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600–1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600–3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P &lt; 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P &lt; 0.00000006), and absence of tumor capsule (P &lt; 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

scholarly journals Snail-1 Overexpression Correlates with Metastatic Phenotype in BRAFV600E Positive Papillary Thyroid Carcinoma

2020 ◽  
Vol 9 (9) ◽  
pp. 2701
Author(s):  
Katarzyna Wieczorek-Szukala ◽  
Janusz Kopczynski ◽  
Aldona Kowalska ◽  
Andrzej Lewinski
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Migration And Invasion ◽  
Malignant Neoplasms ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Metastatic Phenotype ◽  
Mutation Status ◽  
Mesenchymal Transition

The ability of cancer to metastasize is regulated by various signaling pathways, including transforming growth factor β (TGFβ), also implicated in the upregulation of Snail-1 transcription factor in malignant neoplasms. B-type Raf kinase gene (BRAF)V600E, the most common driving mutation in papillary thyroid carcinoma (PTC), induces epithelial to mesenchymal transition (EMT) in thyroid cancer cells through changes in the Snail-1 level, increasing cell migration and invasion. However, little is known about the mechanism of Snail-1 and BRAFV600E relations in humans. Our study included 61 PTC patients with evaluated BRAFV600E mutation status. A total of 18 of those patients had lymph node metastases—of whom 10 were BRAFV600E positive, and 8 negative. Our findings indicate that the expression of Snail-1, but not TGFβ1, correlates with the metastatic phenotype in PTC. This is the first piece of evidence that the upregulation of Snail-1 corresponds with the presence of BRAFV600E mutation and increased expression of Snail-1 in metastatic PTC samples is dependent on BRAFV600E mutation status.

Mixed histiocytosis with BRAF (V600E) mutation and papillary thyroid carcinoma

2019 ◽  
Author(s):  
Francoise Archambeaud ◽  
Pauline Vital ◽  
Gilles Russ ◽  
Isabelle Pommepuy ◽  
Julien Haroche ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid

Aggressive Papillary Thyroid Carcinoma without Brafv600e Mutation

2014 ◽  
Vol 2 (4) ◽  
Author(s):  
Emine Demirbaş ◽  
Mehmet Aşık ◽  
Semra Özdemir ◽  
Hacer Şen ◽  
Fahri Güneş ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Brafv600e Mutation
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