ABSTRACT
Introduction: Ameloblastoma is a benign epithelial odontogenic neoplasm that constitutes approximately 1% of all oral tumors and about 9 to 11% of all odontogenic tumors. They are slow-growing, locally invasive, and demonstrate a potential for metastasis and malignant transformation. The molecular pathogenesis of ameloblastoma is attributed to aberrant activity of the signal transduction pathways relating to developmental stages of odontogenesis including the mitogen-activated protein kinase (MAPK) pathway. The BRAF V600E mutation was identified as the most frequently mutated gene in this neoplasm. Studies have shown that use of BRAF inhibitors in patients diagnosed with ameloblastomas led to a significant reduction in tumor volume. Aims: To detect the expression of BRAF V600E mutation in ameloblastomas in an Indian population using immunohistochemistry. To compare the difference in the occurrence of the BRAF V600E mutation between mandibular and maxillary cases. Materials and Methods: Thirty-three formalin-fixed paraffin-embedded tissues of histopathologically proven cases of ameloblastoma were assessed for the BRAF V600E mutation by immunohistochemistry using the BRAF V600E monoclonal antibody. Patient data such as age, sex, anatomical site, recurrence were documented. Statistical Analysis: The statistical analysis was performed using the Pearson Chi-square test and Student's t-test. Results: The present study revealed a high expression of the BRAFV600E mutation in mandibular cases of ameloblastoma among Indians irrespective of the age, sex, site, recurrence or histological pattern. Conclusions: The identification of this driver mutation opens the possibility of an adjuvant therapeutic modality to reduce the significant facial disfigurement and morbidity following surgical management.
ABSTRACT
ABSTRACT Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, β-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.
ABSTRACT
Objective:To investigate the diagnostic value of thyroid imaging report and data system (TIRADS) combined with BRAF V600E mutation detection in differentiating uncertain thyroid nodules by using fine needle aspiration cytology (FNAC), and to analyze the role of TIRADS classification in screening the nodules needed to be routinely detected for BRAF V600E mutation.Methods:The clinicopathological data of 337 thyroid nodules patients diagnosed with TIRADS classification, FNAC Bethesda classification, BRAF V600E mutation detection and postoperative histopathology from the Second Hospital of Hebei Medical University between January 2018 and August 2021 were retrospectively analyzed. The role of TIRADS classification, FNAC Bethesda classification and BRAF V600E mutation detection alone and the combined detection in the differentiation of benign and malignant thyroid nodules was also analyzed.Results:The postoperative histopathological result was regarded as the gold standard. The sensitivity of TIRADS classification, FNAC Bethesda classification and BRAF V600E mutation for thyroid cancer diagnosis was 76.0%, 88.1% and 80.4% respectively, and the corresponding specificity was 84.0%, 96.0% and 100.0%, respectively. Histologically, 37 (62.7%) of 59 nodules with FNAC uncertainty were malignant nodules after the surgery. The sensitivity and accuracy of BRAF V600E mutation detection in the diagnosis of FNAC uncertain nodules were 51.4% and 69.5%, respectively, while the sensitivity and accuracy of BRAF V600E mutation detection combined with TIRADS classification were 86.5% and 84.7%, respectively. The sensitivity and accuracy of BRAF V600E mutation detection combined with TIRADS classification were both improved ( P values were 0.002 and 0.049, respectively). The positive rate of BRAF V600E mutation in thyroid nodules increased step by step with the rise of risk degree in TIRADS classification, and the type 3 cases were lower than those in type 4a cases [14.3% (1/7) vs. 68.6% (24/35), P = 0.012], and there were no statistically significant differences among the adjacent groups above 4a (all P > 0.05). Conclusions:TIRADS combined with BRAF V600E mutation detection can improve the sensitivity and accuracy in the diagnosis of FNAC uncertain thyroid nodules. The BRAF V600E mutation rate of TIRADS 4a and above nodules is high, so routine detection is recommended.
ABSTRACT
Objective:To Constructing a nomogram based on clinical, ultrasound and BRAF V600E gene for predicting cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC).Methods:The clinical data of 287 patients with PTC (374 malignant nodules) from December 2019 to December 2021 in the First Affiliated Hospital of Hunan Normal University were analyzed retrospectively. Among them, there were 205 nodes with cervical lymph node metastasis and 169 nodes without cervical lymph node metastasis. The echo type, capsule, boundary, shape, number, diameter, location, cystic and solid properties, aspect ratio, blood flow signal, echo distribution, ultrasonic classification, microcalcification and enlarged lymph nodes were observed by ultrasound. The mutation of BRAF V600E gene was detected by fluorescence polymerase chain reaction. The nomograph model for predicting neck lymph node metastasis in patients with PTC was constructed and validated by R3.6.3 software.Results:Univariate analysis result showed that gender, age, microcalcifications, aspect ratio, morphology, blood flow signal, diameter, echo distribution, enlarged lymph nodes, ultrasound classification and BRAF V600E gene were the risk factors for cervical lymph node metastasis in patients with PTC ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that age (<40 years old), ultrasonic classification (≥4a) and diameter (>1 cm) were independent risk factors for cervical lymph node metastasis in patients with PTC ( OR = 2.847, 1.436 and 2.475; 95% CI 1.827 to 4.436, 1.075 to 1.918 and 1.505 to 4.069; P<0.01 or <0.05). The age, ultrasonic classification and diameter were included as predictors for constructing the nomogram model. The receiver operating characteristic curve analysis result shows that the area under the curve predicted by the nomogram model for neck lymph node metastasis in patients with PTC was 0.692 (95% CI 0.631 to 0.753). Conclusions:Nomogram based on age, ultrasonic classification and diameter is of high value in predicting neck lymph node metastasis in patients with PTC.
ABSTRACT
Thyroid Carcinoma, as one of the most common malignant tumors in the endocrine system and head and neck, has a rising incidence rate in the world in recent years, which seriously affects human health. Thyroid carcinoma is often divided into 4 pathological types: papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Among them, papillary carcinoma is the most common with low malignancy and undifferentiated carcinoma is extremely rare with the highest malignancy. BRAFV600E mutation has been found to be closely related to the genesis, development mechanism and prognosis of thyroid carcinoma, and is a current molecular research focus. Clinically, BRAFV600E mutation is often considered as a molecular marker affecting the prognosis of thyroid carcinoma. In this paper, the relevant literature in recent years was reviewed, mainly from the aspects of BRAFV600E mutation and thyroid carcinoma diagnosis, clinicopathological features, guidance of clinical treatment decision, prognosis and so on, to evaluate the clinical application value of BRAFV600E mutation.
ABSTRACT
Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in?depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular?targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular?targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at th
ABSTRACT
Objective:To investigate the value of BRAF V600E mutation combined with 2015 American Thyroid Association (ATA) Guidelines ultrasound (US) pattern in fine-needle aspiration (FNA) cytology of thyroid nodules with atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS).Methods:This study retrospectively enrolled 96 consecutive patients with 101 AUS/FLUS thyroid nodules who underwent preoperative US, FNA, and BRAF V600E mutation analysis. All AUS/FLUS nodules were classified based on US pattern-based risk stratification of 2015 ATA Guidelines. With postoperative pathology as the gold standard, the diagnostic value of BRAF V600E mutation, US pattern and the combination of two methods were compared.Results:Postoperative pathology confirmed 33 benign nodules and 68 malignant nodules. The mutation rates of BRAF V600E in AUS/FLUS nodules was 51.5%. The sensitivity, specificity, and accuracy of BRAF V600E in the diagnosis AUS/FLUS nodules were 72.1%, 90.9% and 78.2%, respectively. The ROC curve demonstrated that the best cut-off of US pattern was high suspicion. The sensitivity, specificity, and accuracy of US pattern in the diagnosis of AUS/FLUS nodules were 63.2%, 81.8% and 69.3%, respectively. The accuracy of US pattern in determining AUS/FLUS nodules without BRAF V600E mutation was 70.6%. The sensitivity, specificity, and accuracy of the combination of two methods in the differential diagnosis of AUS/FLUS nodules were 89.7%, 75.8%, and 85.1%, respectively. The combination had the highest sensitivity ( P<0.05). Conclusions:BRAF V600E mutation has a good diagnostic value for differentiating benign and malignant AUS/FLUS nodules. Combined with US pattern, the differential diagnostic value for AUS/FLUS nodules without BRAF V600E mutation can be improved, and the sensitivity can be raised.
ABSTRACT
Objective:To investigate the clinical features of patients with Langerhans cell histiocytosis (LCH), and analyze the association between BRAF V600E mutation status and clinical features. Methods:A retrospective analysis was carried out for the clinical data of 60 patients with LCH at the Department of Pediatric Oncology, Sun Yat-sen Memorial Hospital between April 2013 and December 2019.Among them, 39 patients undertook BRAF V600E mutation testing, which in paraffin-embedded tissue samples were detected by quantitative real-time PCR (qRT-PCR), and in peripheral blood and/or bone marrow were tested by high-throughput sequencing, for analyzing the correlation between BRAF V600E mutation and clinical characteristics of LCH. Results:(1)Clinical characteristics: the age of 60 LCH patients was (4.08±0.45) years, with 43 male cases and 17 female cases.Patients at young age (≤2 years) and with risk organ (RO+ ) and central nervous system (CNS) risk lesions involvement were concentrated in the multisystem involvement (MS) group ( P<0.05). (2)Therapeutic response after induction therapy: the response to induction therapy was achieved in 28 of 60 treated patients (41.7%) and 32 (53.3%) did not.After excluding stratification factors of treatment regimen, MS ( OR=6.855, 95% CI: 2.077-22.622, P=0.002) and the age≤2 years ( OR=4.944; 95% CI: 1.601-15.275; P=0.005) were risk factors in poor chemotherapy response.RO+ ( OR=8.250, 95% CI: 1.617-42.090, P=0.005) was a significant risk factor for a poor chemotherapy response in JLSG-02 treatment group.Differently, RO+ had no dramatic effect on chemotherapy response in CCHG-LCH-2019 treatment group.(3) BRAF V600E mutation: 39 patients were determined BRAF V600E status, with the positive rate of BRAF V600E mutation in paraffin-embedded tissue samples reaching 70.3%(26 cases). BRAF V600E mutation was not associated with early treatment response, age, sex, MS and RO+ ( P>0.05). However, the positive rate of BRAF V600E in children with MS and CNS risk lesions was higher than the controls, with 76.0% (19 cases) vs.57.1% (8 cases) and 74.1% (20 cases) vs.58.3% (7 cases), respectively.Totally, 3 of 8 cases were positive in bone marrow, with 2 cases of MS, and 1 case of multiple bone invasions, and 1 of 5 cases was positive in peripheral blood, with liver and spleen being involved. Conclusions:LCH patients with age≤2 years, MS and RO+ exhibited a poor response to initial treatment, required for more aggressive treatment strategy.Lesion with activating BRAF V600E mutations suggests that LCH is a clonal disorder.There may be great variability between BRAF V600E mutations and MS as well as CNS risk lesions.In the mutation dataset, part of patients had positive BRAF V600E mutations in bone marrow/peripheral blood.This might suggest a different pathogenesis in such patients, has a certain clinical sense in some aspect.
ABSTRACT
BRAF V600E mutation is a common gene mutation in papillary thyroid carcinoma (PTC) , which is associated with the occurrence, development, and prognosis of PTC. TERT promoter mutations are rare in PTC, but PTC with its mutations is more aggressive and has a worse prognosis. Clinically, a small number of PTC patients have both BRAF V600E mutation and TERT promoter mutations. This article provides a brief overview of the co-mutation of BRAF V600E and TERT promoter and the occurrence and development, clinical diagnosis, surgical strategies, postoperative adjuvant treatment, and prognosis of PTC.
ABSTRACT
Objective: To explore the relationship between TERT promoter mutations and BRAF V600E as well as their coexistence with the clinicopathological features of papillary thyroid cancer (PTC). Methods: A total of 728 patients enrolled in Shanxi Cancer Hospital from December 2014 to December 2016 with PTC were retrospectively analyzed. We reviewed and analyzed the clinical results, pathology records, ultrasound results, and BRAF V600E and TERT status. Results: BRAF V600E mutations were found in 42.3% (308 of 728) of patients, and TERT C228T and C250T promoter mutations were found in 10.7% (78 of 728) and 0.5% (4 of 728) of patients, respectively. The TERT promoter mutation was significantly associated with old age (P=0.034), extrathyroidal invasion (P=0.026), large tumor size (P=0.028), cervical lymph node metastasis (P=0.012), distant metastasis (P=0.001), advanced disease stages (P<0.001), histological type (P=0.003) and recurrence (P=0.002). The BRAF V600E mutation was significantly associated with extrathyroidal invasion (P= 0.001), large tumor size (P<0.001), Hashimoto thyroiditis (P<0.001), distant metastasis (P=0.010), advanced disease stages (P=0.009) and recurrence (P=0.001). The coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, such as old age (P=0.024), extrathyroidal invasion (P=0.022), Hashimoto thyroiditis (P=0.005), the cervical lymph node (P=0.018), and advanced disease stages (P=0.002). Conclusions: Our study demonstrates that BRAF V600E and TERT promoter mutations play a significant role in the aggressiveness of PTC, particularly when the two mutations coexist. The results reveal the significant role of these mutations in the treatment and prognosis prediction of PTC.
ABSTRACT
Introducción: el melanoma representa el 4 por ciento de todos los tumores malignos de la piel, pero es responsable del 80 por ciento de las muertes por cáncer en este sitio. El surgimiento de las terapias dirigidas contra la mutación de BRAF ha cambiado el pronóstico, de allí, la importancia de identificar esta mutación en los pacientes con diagnóstico histológico de melanoma maligno ya que la tasa de mutaciones del oncogén BRAF es alta. Objetivo: describir las implicaciones diagnósticas, terapéuticas y pronósticas de la determinación de la mutación del gen BRAF V600E en el melanoma maligno cutáneo. Método: revisión bibliográfica vía PUBMED con la introducción de los siguientes términos de búsqueda: melanoma, melanoma AND genetics, melanoma AND BRAF mutation, melanoma AND BRAF V600E AND prognosis. Se identificaron 72 publicaciones. Resultados: múltiples estudios han corroborado la alta frecuencia del oncogén BRAF V600E mutado en el melanoma cutáneo, ofreciendo la posibilidad de que a través de la identificación de dicha alteración se pueda contribuir a mejorar el diagnóstico y a garantizar un tratamiento dirigido específicamente contra la actividad de BRAF. Conclusiones: la identificación de la mutación del oncogén BRAF representa un factor pronóstico y puede representar una diana terapéutica eficaz(AU)
Introduction: Melanoma accounts for 4per cent of all malignant skin tumors, but is responsible for 80 per cent of cancer deaths in this site. The emergence of therapies directed against the BRAF mutation has changed the prognosis, hence the importance of identifying this mutation in patients with histological diagnosis of malignant melanoma since the rate of mutations of the BRAF oncogene is high. Objective: to describe the diagnostic, therapeutic and prognostic implications of the determination of the mutation of the BRAF V600E gene in cutaneous malignant melanoma. Method: literature review via PUBMED with the introduction of the following search terms: melanoma, melanoma AND genetics, melanoma AND BRAF mutation, melanoma AND BRAF V600E AND prognosis. 72 publications were identified. Results: multiple studies have corroborated the high frequency of the mutated BRAF V600E oncogene in cutaneous melanoma, offering the possibility that through the identification of this alteration it can contribute to improve the diagnosis and to guarantee a treatment directed specifically against the activity of BRAF. Conclusions: the identification of the BRAF oncogene mutation represents a prognostic factor and may represent an effective therapeutic target(AU)
Introdução: O melanoma é responsável por 4 por cento de todos os tumores malignos da pele, mas é responsável por 80 por cento das mortes por cáncer neste site. O surgimento de terapias direcionadas contra a mutação BRAF alterou o prognóstico, daí a importância da identificação dessa mutação em pacientes com diagnóstico histológico de melanoma maligno, já que a taxa de mutações do oncogene BRAF é alta. Objetivo: descrever as implicações diagnósticas, terapêuticas e prognósticas da determinação da mutação do gene BRAF V600E no melanoma maligno cutâneo. Método: Revisão de literatura via PUBMED com a introdução dos seguintes termos de pesquisa: melanoma, melanoma e genética, melanoma e mutação BRAF, melanoma e BRAF V600E e prognóstico. 72 publicações foram identificadas. Resultados: Estudos múltiplos confirmaram a alta frequência do oncogene BRAF V600E mutante no melanoma cutâneo, oferecendo a possibilidade de que através da identificação de tal alteração pode ajudar a melhorar o diagnóstico e para assegurar um tratamento dirigido específicamente contra a actividade de BRAF. Conclusões: A identificação da mutação oncogênica BRAF representa um fator prognóstico e pode representar um alvo terapêutico eficaz(AU)
Subject(s)
Humans , Prognosis , Nevi and Melanomas/diagnosis , Nevi and Melanomas/therapy , MutationABSTRACT
Objective@#To explore the correlation of ultrasound-guided fine-needle aspiration(US-FNA) combined with BRAF V600E mutation detection and ultrasound features and central cervical lymph nodes metastasis of classic papillary thyroid cancer(PTC) for providing a reliable molecular basis for clinical preoperative evaluation of patients.@*Methods@#Ninty-three cases of patients collected from October 2017 to November 2018 in Gansu Province Hospital were enrolled, who underwent general ultrasonic examination TI-RADS ≥4a, the US-FNA highly suspicious of PTC, thyroid surgery including total thyroidectomy and central cervical lymph node dissection, with the postoperative pathologic results of classical PTC and whether the central cervical lymph node metastasis happened in the patients. Part of the specimen applied HE staining for cytological diagnosis, the other part of specimen was used real-time for detection of BRAF V600E gene mutation by fluorescent quantitative polymerase chain reaction (PCR) method.@*Results@#Univariate analysis showed that the occurrence of cervical lymph node metastasis for classic PTC were significantly correlated with gender(χ2=10.303, P=0.002), BRAF V600E mutation(χ2=31.204, P=0.000) and extrathyroidal invasion(χ2=12.848, P=0.000). Multi-logistic regression analysis showed that BRAF V600E mutation(OR=13.324, 95%CI=4.058-43.744, P=0.000) and extrathyroidal invasion(OR=5.738, 95%CI=1.766-18.643, P=0.004) were the risk predictors of cervical lymph node metastasis of classic PTC. Gender(OR=0.385, 95%CI=0.112-1.324, P=0.130) was not the risk predictor.@*Conclusions@#US-FNA combined with BRAF V600E mutation and extrathyroidal invasion are the risk factors in predicting central cervical lymph node metastasis in classic PTC. Patients with these two risk factors should be elected to undergo prophylactic central cervical lymph node dissection.
ABSTRACT
OBJECTIVE: To investigate the correlation between clinicopathological features and BRAF~(V600E) gene mutation in papillary thyroid carcinoma(PTC). METHODS: The data of 290 cases of PTC admitted from August 2016 to May 2018 in Beijing Tongren Hospital,Capital Medical University were analyzed retrospectively. All the cases of PTC were examined by BRAF~(V600E) immunohistochemistry after operation. Mutation positive group included 192 cases. Mutation negative group included 59 cases and partial mutation group included 39 cases. The cases of partial mutantion were excluded. The clinicopathological differences between the two groups were compared. RESULTS: By statistical analysis,there was a statistical difference between two groups in the invasion of the capsule(P<0.05). In the two groups(microcarcinoma and non-microcarcinoma),there was the same result.There was no statistical difference in other indexes. CONCLUSION: In patients with PTC,BRAF~(V600E) gene mutation is not associated with the clinicopathological features of the PTC. Patients with non-BRAF~(V600E) gene mutations are more likely to invade the membranes of microcarcinomas and non-microcarcinomas.
ABSTRACT
Objective@#To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS).@*Methods@#We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases.@*Results@#Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis.@*Conclusions@#FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.
ABSTRACT
Objective To evaluate the diagnostic efficacies of contrast-enhanced ultrasound(CEUS) combined with BRAF V600E mutation detection in ultrasound-guided fine-needle aspiration cytology of thyroid nodules with atypia of undetermined significance . Methods A total of 129 thyroid nodules underwent the examinations of CEUS and BRAF V600E mutation were analyzed retrospectively . With surgical pathology as the gold standard ,ROC curve was used to investigate the diagnostic values of CEUS , BRAF V600E and the combination of the two methods . Results The sensitivity ,specificity and accuracy of CEUS and BRAF V600E gene detection for thyroid nodules with atypia of undetermined significance diagnosed by ultrasound-guided fine-needle aspiration biopsy were 86 .7％ ,83 .3％ ,85 .3％ and 72 .0％ , 100％ ,83 .7％ ,respectively . The sensitivity and accuracy of CEUS were higher than those of BRAF V 600E gene detection ( all P < 0 .001 ) ,however its specificity was lower than BRAF V 600E with statistically significance( P < 0 .001) ,those of the combined test of CEUS and BRAF V600E mutation analysis were 94 .7％ ,83 .3％ ,89 .9％ ,respectively . The combination of two methods had the highest diagnostic efficacy , with statistically difference ( P <0 .001) ,and the area under the ROC curve ( AUC) was higher than that for each test(0 .951 vs 0 .860 vs 0 .901) . Conclusions The combined test of CEUS and BRAF V600E mutation has a higher diagnostic efficacy for cytologically indeterminate thyroid nodules compared with CEUS or BRAF V600E mutation alone .
ABSTRACT
Objective To explore the correlation of ultrasound-guided fine-needle aspiration(US-FNA) combined with BRAF V600E mutation detection and ultrasound features and central cervical lymph nodes metastasis of classic papillary thyroid cancer(PTC)for providing a reliable molecular basis for clinical preoperative evaluation of patients.Methods Ninty-three cases of patients collected from October 2017 to November 2018 in Gansu Province Hospital were enrolled,who underwent general ultrasonic examination TI-RADS ≥4a,the US-FNA highly suspicious of PTC,thyroid surgery including total thyroidectomy and central cervical lymph node dissection,with the postoperative pathologic results of classical PTC and whether the central cervical lymph node metastasis happened in the patients.Part of the specimen applied HE staining for cytological diagnosis,the other part of specimen was used real-time for detection of BRAF V600E gene mutation by fluorescent quantitative polymerase chain reaction (PCR) method.ResultsUnivariate analysis showed that the occurrence of cervical lymph node metastasis for classic PTC were significantly correlated with gender(χ2=10.303,P =0.002),BRAF V600E mutation(χ2=31.204,P =0.000)and extrathyroidal invasion(χ2=12.848,P =0.000).Multi-logistic regression analysis showed that BRAF V600E mutation(OR=13.324,95％CI=4.058-43.744,P =0.000) and extrathyroidal invasion(OR=5.738,95％CI=1.766-18.643,P=0.004)were the risk predictors of cervical lymph node metastasis of classic PTC.Gender(OR=0.385,95％CI=0.112-1.324,P =0.130) was not the risk predictor.Conclusions US-FNA combined with BRAF V600E mutation and extrathyroidal invasion are the risk factors in predicting central cervical lymph node metastasis in classic PTC.Patients with these two risk factors should be elected to undergo prophylactic central cervical lymph node dissection.
ABSTRACT
Objective@#To evaluate the value of ultrasound-guided fine needle aspiration(US-FNA) combined with detection of BRAF V600E and thyroid imaging reporting and data system(TI-RADS) in diagnosis of benign and malignant thyroid nodules.@*Methods@#In this study, 123 operative thyroid nodules from 114 patients who underwent US-FNA and detection of BRAF V600E were enrolled. TI-RADS was apply for the classification of each nodule before surgery. Specimens from each nodule were subjected for hematoxylin and eosin (HE) staining and cytological diagnosis and detection of BRAF V600E mutation.@*Results@#①BRAF V600E mutation was found in 71 (71/123) nodules with histologic confirmation of papillary-thyroid carcinoma, 58 of which were cytologically diagnosed as carcinoma and 13 were indeterminate. Compared with the postoperative pathological results, US-FNA combined with BRAF V600E could improve the sensitivity and accuracy of diagnosis to thyroid nodules compared with individual US-FNA, and the difference was statistically significant(P<0.001). ②The mutation rate of BRAF V600E was associated with thyroid capsular invasion(χ2=8.44, P=0.004), and combined with TI-RADS could indicate the high-risk of this invasion. ③Among 123 operative nodules, 18 nodules were BRAF V600E negative and cytologically diagnosed as indetermination, 10 of which were TI-RADS 3b or above. After thyroidectomy, 6 nodules were confirmed as papillary-thyroid carcinoma, 1 nodule was thyroid follicular carcinoma, and 3 nodules were benign ones.@*Conclusions@#US-FNA combined with detection of BRAF V600E and TI-RADS can improve the diagnostic accuracy and decrease the misdiagnosis in indeterminate nodules.
ABSTRACT
Objective@#To evaluate the diagnostic value of BRAF V600E mutation combined with shear wave elastography(SWE) for thyroid nodules of Bethesda Ⅲ diagnosed by fine-neddle aspiration(FNAC).@*Methods@#One hundred and seventeen thyroid nodules diagnosed as Bethesda Ⅲ in the department of ultrasound and confirmed by BRAF V600E gene detection, SWE examination and surgery were collected. BRAF V600E detection, SWE examination and both combined with pathological results were using to retrospective analysis.@*Results@#There were 75 benign nodules and 42 malignant nodules according to pathology. Sensitivity and negative predictive value of BRAF V600E combined with SWE were higher than single BRAF V600E mutation detection and SWE with statistically significant(P=0.01, 0.001; P=0.029, 0.01, respectively). There were no statistically differences between single BRAF V600E mutation detection and SWE for Bethesda Ⅲ nodules(P=0.483, 0.645).@*Conclusions@#BRAF V600E mutation detection combined with SWE can improve the sensitivity and negative predictive value in the diagnosis of Bethesda Ⅲ thyroid nodules.
ABSTRACT
Objective@#To investigate the clinicopathologic characteristics and BRAF V600E mutation of brain tumors associated with epilepsy.@*Methods@#Totally 250 patients with brain tumors associated with epilepsy were included from March 2008 to August 2017 retrospectively at Sanbo Brain Hospital, Capital Medical University.The clinical manifestations, histological features and BRAF V600E mutation results were collected and analyzed.@*Results@#There were 132 males and 118 females, and the male to female ratio was 1.1∶1.0. The age of patients ranged from 2 to 67 years(mean 22 years). The tumors had obvious local space occupying effect on MRI. The temporal lobe was the most common site (44.4%, 111/250). There were 58.4% (146/250) of ganglioglioma (GG), 24.0% (60/250) of dysembryoplastic neuroepithelial tumor (DNT), 12.8% (32/250) of pleomorphic xanthoastrocytoma(PXA), 4.0% (10/250) of angiocentric glioma (AG) and 0.8% (2/250) of papillary glioneuronal tumor (PGNT). Mixed GG, PXA and DNT morphological structures were found in 9 of patients. Among 250 cases, 35 cases were accompanied by focal cortical dysplasia(FCD). BRAF V600E was seen in 43 of 74 (58.1%) GG and 13 of 28 (46.4%) PXA. The most common pathologic grade of GG, DNT, AG and PGNT was WHO I. Some of the tumor cells from GG (34 cases) showed higher proliferative activity (WHO Ⅱ/Ⅲ). Most cases of PXA were WHOⅡand high proliferative activity was seen in nine cases.@*Conclusions@#The association of low-grade glioneuronal tumors with intractable epilepsy was well-recognized. The most common low-grade glioneuronal tumors were GG.GG may occur in any part of the central nervous system, with a predilection for temporal lobe. Each type of low-grade glioneuronal tumors has its own unique histological morphology, but some may show complex features with 2 or 3 mixed components. The occurrence of BRAF V600E mutations in GG is common, and their detection may be valuable for the diagnosis and treatment in GG.
ABSTRACT
BACKGROUND AND OBJECTIVES: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). MATERIALS AND METHODS: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. RESULTS: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p < 0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p < 0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p < 0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p < 0.001) and GLUT-1 gene (r=−0.204, p < 0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. CONCLUSION: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.