BRAFV600E Mutation Analysis Research Articles

Development of Novel Mutation-Specific Droplet Digital PCR Assays Detecting TERT Promoter Mutations in Tumor and Plasma Samples

Detecting mutations in the plasma of patients with solid tumors is becoming a valuable method of diagnosing and monitoring cancer. The TERT promoter is mutated at high frequencies in multiple cancer types, most commonly at positions -124 and -146 (designated C228T and C250T, respectively). Detection of these mutations has been challenging because of the high GC content of this region (approximately 80%). We describe development of novel probe-based droplet digital PCR assays that specifically detect and quantify these two mutations, along with the less common 242-243 CC>TT mutation, and demonstrate their application using human tumor and plasma samples from melanoma patients. Assay designs and running conditions were optimized using cancer cell line genomic DNAs with the C228T or C250T mutations. The limits of detection were 0.062% and 0.051% mutant allele fraction for the C228T and C250T assays, respectively. Concordance of 100% was observed between droplet digital PCR and sequencing-based orthogonal methods in the detection of TERT mutant DNA in 32 formalin-fixed, paraffin-embedded melanoma tumors. TERTmutant DNA was also identified in 21 of 27 plasma samples (78%) from patients with TERTmutant tumors, with plasma mutant allele fractions ranging from 0.06% to 15.3%. There were no false positives in plasma. These data demonstrate the potential of these assays to specifically detect and quantify TERTmutant DNA in tumors and plasma of cancer patients.

Central nervous system-predominant Erdheim–Chester disease mimicking meningioma responding to BRAF inhibitor therapy: the importance of molecular diagnosis and targeted therapy in rare neoplastic disorders

Erdheim–Chester disease (ECD) is a rare multi-system, non-Langerhans cell histiocytic disorder (NLCHD) with only a few hundred cases reported in the literature. Its diverse clinical manifestations require a high level of diagnostic suspicion. BRAFV600E mutation analysis is of critical significance, as it has implications for targeted therapy with BRAF inhibitors such as vemurafenib and dabrafenib. We report a case of symptomatic, central nervous system (CNS)-predominant ECD initially presenting with CNS mass lesions mimicking meningiomas on imaging and prominent periorbital xanthogranulomas. CNS presentation of ECD, although not infrequent, bears particular significance here from a therapeutic point of view, since only partial debulking was possible owing to anatomical complexities. Radiological evaluation following surgery showed no significant change in the size of the lesions. Targeted therapy was commenced following histopathology, immunohistochemistry (IHC), and molecular testing, resulting in marked improvement of clinical symptoms and tumor regression. Thus, diagnostic accuracy was imperative for symptomatic relief in this rare but aggressive neoplasm with a complex clinical presentation and misleading initial radiological impressions, bearing an otherwise grim prognosis.

Role of Strain Elastography and Shear-Wave Elastography in a Multiparametric Clinical Approach to Indeterminate Cytology Thyroid Nodules.

BackgroundIn thyroid nodules with indeterminate cytology, further clinical assessment aimed at ruling out malignancy is often mandatory. Ancillary imaging techniques and genetic mutation analysis can improve the risk stratification of such lesions, thereby facilitating the clinician’s decision to undertaken surgery or simple follow-up. The aim of this study was to evaluate the diagnostic performance of shear-wave elastography (SW), strain elastography (ELX 2/1), conventional ultrasound (US), contrast-enhanced ultrasound (CEUS), and BRAF V600E mutation analysis in the aforementioned lesions.Material/MethodsWe enrolled 81 patients, each with 1 indeterminate-cytology thyroid nodule. Thyroid function, thyroperoxidase antibodies and calcitonin were known in each case. SW, ELX 2/1, US, CEUS, and BRAF mutation analysis were subsequently performed, followed by a second FNAB. If the lesion was not downgraded to benign, surgery was recommended and histological reports collected.ResultsThere were 28 nodules (34%) that proved benign on the second FNAB; 38 nodules (47%) underwent surgery (17 benign, 21 malignant), and 15 nodules (19%) refused surgery. The only techniques related to histological outcome were US (AUC=0,766), ELX 2/1 (AUC=0.701), and BRAF analysis (AUC=0.762). ELX 2/1 and SW reports were not correlated with each other (P=0.45). A scoring system taking into account all the variables considered performed better than the single variables alone (AUC=0.831).ConclusionsIn indeterminate-cytology thyroid lesions, repeating FNAB can avoid unnecessary surgery. ELX 2/1 seems to perform better than SW in distinguishing malignancy; these techniques could, however, be complementary in describing such lesions. A multiparametric approach appears the most accurate in predicting nodule histology.

Utility of including BRAF mutation analysis with ultrasonographic and cytological diagnoses in ultrasonography-guided fine-needle aspiration of thyroid nodules

This study investigated the role of BRAF mutation analysis in thyroid fine-needle aspiration (FNA) samples compared to ultrasonographic and cytological diagnoses. A total 316 patients underwent ultrasonography (US)-guided FNA with BRAFV600E mutation analysis to diagnose thyroid nodules. One hundred sixteen patients with insufficient US images (n = 6), follow-up loss (n = 43), or unknown final diagnosis (n = 67) were excluded from the study. Comparisons between US diagnoses, cytological diagnoses, and BRAF mutation analysis were performed. Of 200 thyroid nodules, there was US diagnosis with 1 false negative and 11 false positive cases, cytological diagnosis with 10 false negative and 2 false positive cases, and BRAFV600E mutation analysis with 19 false negative and 2 false positive cases. The sensitivity, specificity, positive and negative predictive values, and accuracy of BRAFV600E mutation analysis were 83.2%, 98.1%, 97.5%, 86.6%, and 91%, respectively. Of the 18 nodules with Bethesda category III, 9 were true positive, 6 were true negative, 3 was a false negative, and none were false positive on BRAF mutation analysis. In conclusion, we recommend that BRAFV600E mutation analysis only be performed for evaluating thyroid nodules with Bethesda category III, regardless of US diagnosis.

Diagnostic value of BRAFV600E mutation analysis in fine needle aspiration for evaluation of thyroid nodules

Objectives Ultrasound-guided fine-needle aspiration (FNA) is routinely used in the evaluation of thyroid nodules. However, it has several pitfalls, as has been noted in nondiagnostic and indeterminate cases. This study aims to investigate the value of BRAF V600E mutation co-testing in FNA cytology. Method A total of 310 patients underwent BRAF V600E mutation co-testing in FNA cytology on thyroid nodules between June 2013 and June 2014. Of the 310 patients, 69 patients who had undergone a surgery for thyroid nodules were included in this study. The presence of the BRAF V600E mutation was determined by allele-specific polymerase chain reaction amplification of exon 15 of the BRAF gene. Results Of 69 cases, 33 (47.8%) were BRAF V600E mutation positive. The BRAF V600E mutation was not significantly associated with high-risk features such as tumor size, lymph node metastasis, and pathological stage. The respective diagnostic performance of FNA ( P = 0.02), BRAF V600E mutation ( P = 0.03), and ultrasonographic ( P = 0.00) findings was statistically significant. The sensitivity, specificity and positive predictive value of FNA was 64.9%, 83.3%, and 94.8%. The sensitivity, specificity and positive predictive value of BRAF V600E mutation was 56.1%, 91.7%, and 96.9% and the US features was 91.2%, 91.7%, and 98.1% respectively. However, sensitivity of FNA with BRAF V600E mutation (77.2%) was lower than FNA with US (92.9%) and combination all together (92.9%). Conclusion In this study, we found that US features were the most useful in preoperative differential diagnosis of thyroid nodules. BRAF V600E mutation co-testing in FNA cytology was also useful for diagnosis of thyroid tumors.

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P=0.0002), especially solid type (30.6 vs. 3.6%, P=0.0061); medullary morphology (19.4 and 0%, P=0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P=0.042), and PD-L1 expression (25.0 vs. 3.6%, P=0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P=0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P=0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

BRAFV600E mutation and DNA ploidy determination in fine needle aspiration biopsy of papillary thyroid microcarcinoma in a Chinese population

This study aimed to evaluate the diagnostic value of BRAFV600E mutation and DNA ploidy determination for Papillary Thyroid Micro-Carcinoma (PTMC) through fine-needle aspiration. Clinical data, including histology, patient population statistics and clinical results were gathered. Patients’ thyroid-micro-lesions were made into FNA-stained smears, DNA was extracted from the smears for different cytological diagnoses. BRAFV600E mutation was detected by Amplification Refractory Mutation System (ARMS). DNA ploidy determination of PTMC was detected by DNA quantitative analyser. All surgical cases were collected for histopathological diagnosis. BRAFV600E mutation was identified in 168 of 180 (93.3%) of PTMC, 0/9 of thyroid follicular carcinomer and 0/1389 of benign thyroid nodules. 127/180 (70.5%) patients got a definitive diagnosis of PTMC when only use cytology. 177/180 (98.3%) patients got a definitive diagnosis of PTMC by a combination of cytology and BRAFV600E mutation analysis (p<0.05). DNA ploidy determination showed no abnormal on papillary thyroid microcarcinoma. BRAFV600E mutation could be only detected in Papillary Thyroid Carcinoma (PTC) patients and is the most common oncogenic alteration in PTC patients. Thus BRAFV600E mutation is a genetic marker of PTMC. BRAFV600E mutation analysis via fine-needle aspiration improved 27.8% of the diagnosis rate of PTMC when combined with cytology.

Presurgical Screening of Fine Needle Aspirates from Thyroid Nodules for BRAF Mutations: A Prospective Single Center Experience.

Objective:Analysis of BRAF V600E mutation in thyroid fine needle aspirates (FNA) is an important adjunct to cytology, particularly among FNA placed in the “indeterminate category.” However, such a prospective evaluation of FNA obtained from patients with thyroid nodules has been lacking from India.Material and Methods:FNA from 277 patients were prospectively evaluated for BRAF mutations by Sanger's sequencing. A subset of 30 samples was also analyzed by pyrosequencing using the PyroMark BRAF mutation kit.Results:Overall, 27.2% of FNA samples were positive for mutations including 19 (35.8%) of the 53 histologically confirmed papillary thyroid carcinoma (PTC), 2 of the 25 follicular variants of PTC, and 1 anaplastic thyroid carcinoma. Only 1 (2.7%) of the 37 samples in the atypia of undetermined significance/follicular lesion of unknown significance category was BRAF positive. The sensitivity of cytology improved marginally from 67.1% to 68.3% when evaluated with BRAF. Further, a comparison of the clinicopathological characteristics of BRAF positive and negative PTCs showed a significant association (P = 0.05) between lymph node metastasis and BRAF positivity.Conclusion:BRAF positivity was lower than that reported from East Asia with the test being useful in confirming malignancies among the suspicious of malignancy and malignant categories.

Prevalence ofBRAFV600EMutation in Follicular Variant of Papillary Thyroid Carcinoma and Non-Invasive Follicular Tumor with Papillary-Like Nuclear Features (NIFTP) in aBRAFV600EPrevalent Area

BackgroundBRAFV600E mutation status and prevalence of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been reported in Korea. The aim of this study was to investigate the significance of the BRAFV600E mutation in the follicular variant of papillary thyroid carcinoma (FVPTC) and to determine the prevalence of NIFTP in BRAFV600E mutation-prevalent Korean patients.MethodsThis study retrospectively analyzed 1,417 consecutive patients who underwent total thyroidectomy with routine prophylactic central lymph node dissection for papillary thyroid carcinoma (PTC). BRAFV600E mutation analysis was performed routinely using multiplex polymerase chain reaction by applying dual priming oligonucleotide. Clinicopathological characteristics and ultrasonographic findings were compared between BRAFV600E mutation-positive and -negative groups for FVPTC. Pathologists reviewed the pathology slides according to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP.ResultsThe prevalence of the BRAFV600E mutation in all subtypes of PTC was 61.0% (861/1,411). FVPTC presented a BRAFV600E mutation rate of 27.3%. The FVPTC patients with BRAFV600E mutation were older than those with no BRAFV600E mutation (P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411) and the proportion of NIFTP among FVPTC was 9.1% (2/22).ConclusionThe BRAFV600E mutation is prevalent in Korean patients with FVPTC in a region with high frequency of the BRAFV600E mutation and very low prevalence of NIFTP compared with that reported in western studies.

History and Practice of Thyroid Fine-Needle Aspiration in China, Based on Retrospective Study of the Practice in Shandong University Qilu Hospital.

Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAFV600E mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.

Erdheim-Chester disease: atypical presentation of a rare disease

We report the clinical case of an adult patient referred to our hospital because of trismus due to a tumour in the right infratemporal and pterygomaxillary fossa. He referred hyporexia,...

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review.

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAFV600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAFV600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm.

A novel cytogenetic and molecular characterization of renal metanephric adenoma: Identification of partner genes involved in translocation t(9;15)(p24;q24)

Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized. Recent data suggest that 90% of MA have BRAFV600E mutations; the genetics of the remaining 10% are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported. However, the potential role of the KANK1 gene, which lies near the breakpoint of the short arm of chromosome 9p24, in the etiology of MA was not examined. We identified the same cytogenetic aberration utilizing molecular cytogenetic techniques in a 22-year-old female patient, and further investigated the genes involved in the translocation that might have contributed to tumorigenesis. A series of fluorescence in situ hybridization (FISH) probes identified the rearranged genes to be KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Mate-Pair genome sequencing validated the balanced translocation between 9p24.3 and 15q25.3, involving genes KANK1 and NTRK3, respectively. BRAFV600E mutational analysis was normal. Our findings indicate that gene fusions may be one mechanism by which functionally relevant genes are altered in the development of MA. Molecular and cytogenetic analyses have elucidated a novel genetic aberration, which helps to provide a better understanding of this genomic change and assist in diagnosis and classification of new subgroups/entities in metanephric adenomas.

Pathologic Characteristics, Natural History, and Prognostic Implications of BRAFV600E Mutation in Pediatric Papillary Thyroid Carcinoma.

The BRAFV600E mutation is the most common genetic aberration in papillary thyroid cancer (PTC), found in up to 68% of PTC in adults where it is associated with aggressive features. The incidence of this mutation in pediatric PTC is less frequent, reported as 0%-20% in the past and up to 63% in one recent series. Data suggest the mutation is not associated with an aggressive course in children; however, there are limited numbers of reported case series, so the prognostic implications remain poorly understood. The aim of this retrospective study was to examine the histologic characteristics and clinical outcomes of BRAF positive pediatric PTC at a single institution. A 12-year retrospective review of all thyroidectomies performed at a tertiary medical center identified 59 pediatric cases with a surgical pathology diagnosis of PTC. Fifty patients had BRAFV600E mutation analysis data and were selected for further study. BRAFV600E mutations were present in 48% of cases (n = 24) and absent in 52% (n = 26). The molecular characteristics of the BRAF negative cases will further be evaluated in future studies. BRAF positive cases occurred in patients who were on average older than the BRAF negative patients. Classic histology PTC was present in both BRAF positive and negative cases; however, only cases with classic PTC histology were positive for the mutation. No patients died and BRAF mutation was not associated with an increased recurrence rate. Our study supports BRAFV600E is more common in children than previously thought and does not portend a more aggressive clinical course.

Lack of Association of B-type Raf Kinase V600E Mutation with High-risk Tumor Features and Adverse Outcome in Conventional and Follicular Variants of Papillary Thyroid Carcinoma.

Introduction:Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome.Study Design:Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue.Results:Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome.Conclusion:BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.

Role and relevance of BRAF mutations in risk stratifying patients of papillary thyroid cancers along with a review of literature.

Molecular markers are increasingly being explored as a potential diagnostic and prognostic tool in patients with well-differentiated thyroid cancers and B-type Raf kinase (BRAF) V600E mutation has received a wide attention in this regard. Many clinical studies have demonstrated an association of BRAF V600E mutation with aggressive clinicopathologic characteristics and high tumor recurrence and mortality in patients with papillary thyroid cancers. Papillary thyroid cancers has been abbreviated and PTCs. The present single center study aims to assess the biological behavior of conventional papillary thyroid cancers. (PTC) with somatic BRAF V600E mutation. Patients who were managed for well differentiated thyroid cancers during 2005-2006 were included in the study. BRAF V600E mutation analysis was done by real time polymerase chain reaction after extracting genomic DNA from the representative archived formalin fixed paraffin embedded tumor tissue. Of the 79 patients of well-differentiated thyroid cancers included in the study, 31% harbored BRAF V600E mutation; the mutation prevalence was 39.6% in the cohort of conventional PTCs. Our study emphatically states that BRAF V600E mutation status is a significant predictor of adverse outcomes in patients with conventional PTCs. Our study further suggests a possible risk-stratified approach using age, BRAF V600E mutation status, and extrathyroidal spread, and this approach can be used to personalize the management of patients with conventional PTCs. The result of our study adds to the growing consensus that BRAF V600E mutational status should be analyzed in correlation with other molecular and clinicopathological prognostic factors for a better risk stratification.

Differences in global DNA methylation of testicular seminoma are not associated with changes in histone modifications, clinical prognosis, BRAF mutations or gene expression

Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate, patchy and hyper-methylated, respectively. A selected subset representing each level of DNA methylation and the TCam2 seminoma cell line were subsequently analysed for a range of other epigenetic marks (6 histone marks and 5-hydroxymethylcytosine), the presence of the BRAF V600E de novo mutation, differences in the transcriptome and finally correlated to the clinical outcome. We did not identify any histone marks or hydroxymethylation levels that correlated with the methylation level of the genome. Some histone marks, however, showed a great variation while others were found at the same level in all the investigated seminomas. We did not identify any tumours with the BRAF V600E mutation and transcriptome analysis revealed no significant differences between hypo- and hyper-methylated seminomas. Similarly, no obvious differences in the clinical manifestation of the patients representing hypo- or hyper-methylated seminomas were identified. The level of DNA methylation in testicular seminomas consequently seems secondary to the manifestation of the tumour phenotype.

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF V600E mutation.

BRAF V600E mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF V600E on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF V600E mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p < 0.005). Furthermore, 20 % of the wild types showed weak monocarboxylate transporter 1 nuclear expression associated to a less aggressive behavior. The analysis of glucose trasporter-1 and carbonic anhidrase did not highlight any statistical significance (p > 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF V600E mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.

Analysis of BRAFV600E Mutation and Persistence of Papillary Thyroid Cancer after Total Thyroidectomy and Routine Central Neck Dissection

Purpose The aim of this study is to investigate the predictive value of BRAF V600E mutation for the persistence of papillary thyroid cancer (PTC) after total thyroidectomy and routine central neck dissection. Patients and Methods We collect the clinicopathological data of 288 PTC patients with total thyroidectomy (TT) and routine central neck dissection (CND), and analyzed the relationship between BRAFV600E mutation status and the rate of elevated non-stimulated thyroglobulin (NSTg) value. And we also collect the clinicopathological data of 370 PTC patients who needed radio iodine ablation(RIA) after TT and routine CND, and analyzed the relationship between BRAFV600E mutation status and the rate of elevated stimulated Tg (STg)value before RIA. The clinicopathological data included gender, age at diagnosis, multifocality, bilaterality, tumor size, extrathyroidal invasion, and lymph node status of these patients. All the patents were diagnosis as PTC before operation by the combination with ultrasonograph and FNA (fine needle asperation). Results BRAFV600E mutation is not associated with the elevated rate of elevated Tg value after TT and routine CND. Conclusions BRAF V600E mutation is not an independent predictive factor for the persistence of papillary thyroid cancer (PTC) after TT and routine CND.

The follicular variant of papillary thyroid carcinoma: characteristics of preoperative ultrasonography and cytology.

Purpose:The goal of this study was to validate the ultrasonography (US) and cytopathological features that are used in the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) and to characterize the role of BRAFV600E mutation analysis in the diagnosis of FVPTC.Methods:From May 2012 to February 2014, 40 thyroid nodules from 40 patients (mean age, 56.2 years; range, 26 to 81 years) diagnosed with FVPTC were included in this study. The US features of the nodules were analyzed and the nodules were classified as probably benign or suspicious for malignancy. Twenty-three thyroid nodules (57.5%) underwent BRAFV600E mutation analysis. Clinical information and histopathologic results were obtained by reviewing the medical records of the patients.Results:Thirty nodules (75.0%) were classified as suspicious for malignancy, while 10 (25.0%) were classified as probably benign. Seven of the eight nodules (87.5%) with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology showed suspicious US features, while one of the two nodules (50.0%) with follicular neoplasm cytology presented suspicious US features. Five of the 23 nodules (21.7%) that underwent BRAFV600E mutation analysis had positive results, all of which were diagnosed as suspicious for malignancy or malignant based on cytology. None of the nodules with benign, AUS/FLUS, or follicular neoplasm cytology were positive for the BRAFV600E mutation.Conclusion:US features allow nodules to be classified as suspicious for malignancy, and the presence of suspicious US features in nodules with ambiguous cytology may aid in the diagnosis of FVPTC. BRAFV600E mutation analysis is of limited value in the diagnosis of FVPTC.