Highly accurate NGS-based multi-gene testing in the diagnosis of thyroid nodules with indeterminate cytology.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13579-e13579
Author(s):  
Yuntao Song ◽  
Bin Zhang ◽  
Tonghui Ma
Keyword(s):  
Next Generation Sequencing ◽  
Mutation Analysis ◽  
Predictive Value ◽  
Thyroid Nodules ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Gene Testing ◽  
Indeterminate Cytology ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e13579 Background: Thyroid nodules are highly prevalent, Fine-needle aspiration (FNA) is the standard pre-operative tool for diagnosis. However, some of the samples are classified as indeterminate, which leads to unnecessary surgery. BRAF V600E mutation is often used as a diagnostic marker for thyroid cancer, and it is highly specific for papillary thyroid carcinoma (PTC). But BRAF mutation is rarely occurred in thyroid nodules with indeterminate cytology. To diagnose the indeterminate thyroid nodules precisely, some NGS-based multi-gene testing panel has been developed and clinically used in America and Europe, but rare research was reported in China. In this study, we evaluated the value of a next-generation sequencing (NGS) panel to cancer diagnosis in indeterminate thyroid nodules. Methods: From February 2018 to September 2018, 360 patients with thyroid nodules who underwent FNA at Peking University Cancer Hospital were enrolled. And the FNA samples with indeterminate cytology were evaluated using a next-generation sequencing (NGS) assay, including 16 genes analyzed for point mutations and 26 types of gene fusions. Diagnostic performance of this multi-gene testing panel was compared with BRAF V600E single gene mutation analysis. Results: 141 nodules were cytologically indeterminate among 360 patients on FNA biopsy, 72 of which were resected and analyzed by NGS successfully. Histologic analysis after surgery revealed 41 (56.9%) cancers in these 72 patients. The multi-gene testing assay could classify 30/41 cancers correctly, showing a sensitivity of 73.2%, specificity of 96.8%, positive predictive value of 96.8%, and negative predictive value of 73.2%. The diagnostic accuracy of the multi-gene testing was significantly higher than the BRAF V600E mutation analysis (83.3% vs 73.6%, x2= 31.588, p < 0.01). Conclusions: Our study demonstrated that the multi-gene testing provided both high sensitivity and high specificity for cancer detection in thyroid nodules with indeterminate cytology, and its accuracy was much higher than BRAF V600E mutation test.

scholarly journals Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules

2017 ◽  
Vol 142 (2) ◽  
pp. 178-183 ◽  
Author(s):  
Maren Y. Fuller ◽  
Dina Mody ◽  
April Hull ◽  
Kristi Pepper ◽  
Heather Hendrickson ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Thyroid Nodules ◽  
Gene Mutations ◽  
Braf V600e ◽  
Molecular Diagnostic ◽  
Thyroid Malignancy ◽  
Next Generation ◽  
Fine Needle ◽  
Thyroid Fna ◽  
Generation Sequencing

Context.— Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. Objective.— To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. Design.— A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. Results.— Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. Conclusions.— Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

Targeted next-generation sequencing in papillary thyroid carcinoma of Chinese Han population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17574-e17574
Author(s):  
Jie Liu ◽  
Huizheng Li ◽  
Rong Du ◽  
Nan Fang ◽  
Jingbo Zhang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Next Generation Sequencing ◽  
Papillary Thyroid Carcinoma ◽  
Gene Mutations ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Chinese Han ◽  
Han Population ◽  
Generation Sequencing

e17574 Background: Papillary Thyroid Carcinoma (PTC) is the most common type of thyroid cancer. Developments in next-generation sequencing (NGS) technology can help to disclose the genotype of PTC in the Chinese Han population. Methods: A total of 50 patients with PTC who underwent thyroidectomy in 2015-2018 at the Affiliated Dalian Friendship Hospital of Medical University were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 57 thyroid cancer-associated genes were amplified, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: A total of 591 mutations were detected in 50 samples, including 514 missense mutations (87%), 39 frameshift mutations (6.6%), 22 stop-gain (3.7%) and 16 indel (2.7%) variants. Among them, only 64 mutations have been studied with cancer clinical relevance. The BRAF V600E mutation was present in 42 of 50 (84%) patients, and was the most common mutation. The CHEK2 mutation was present in 27 of 50 (54%) patients. The 10 most important genes with mutations included AKT1 (34%), EIF1AX( 30%), ATM (20%) , MED12 (18%) , NF1 (18%), RET (18%), RBM10 (16%) and TERT (12%). Among them, the CHEK2, AKT1 and EIF1AX mutations were always concomitant with the BRAF V600E mutation, which is controversial to previous studies. Only two samples had no mutation tested. The medium mutation is 11 muts/sample. Six samples had more than 10 occurrences of gene mutations. However, the mutation burden has no relevance to lymph node metastasis or other pathological prognostic factors. Conclusions: BRAF V600E is the most common and important mutation in PTC, but there are also many other genes that mutate in this disease. The gene mutation in PTC varies in different patients, but no relevance between pathological factors and gene mutations have been founded . However, the discovery of the gene mutation spectrum in the Han Chinese population with PTC could enhance the understanding of this disease’s clinical behavior.

scholarly journals Role of Ultrasonographic/Clinical Profile, Cytology, and BRAF V600E Mutation Evaluation in Thyroid Nodule Screening for Malignancy: A Prospective Study

2012 ◽  
Vol 97 (7) ◽  
pp. 2354-2361 ◽  
Author(s):  
Martina Rossi ◽  
Mattia Buratto ◽  
Stefania Bruni ◽  
Carlo Filieri ◽  
Federico Tagliati ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mutation Analysis ◽  
Braf Mutation ◽  
Thyroid Nodules ◽  
Braf V600e Mutation ◽  
Diagnostic Sensitivity ◽  
Braf V600e ◽  
Additional Contribution ◽  
Papillary Thyroid ◽  
Diagnostic Potential

Abstract Context: Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the most reliable nonsurgical test for distinguishing benign from malignant thyroid nodules. However, there is no consensus on which nodules should undergo FNAB. Aims: The aims of this study were to evaluate the utility of US-guided FNAB in the diagnostic assessment of nodules with or without clinical/US features suggestive for malignancy and to investigate the additional contribution of BRAF V600E mutation analysis in the detection of differentiated thyroid cancer. Design and Methods: Thyroid cytoaspirates from 2421 nodules at least 4 mm in diameter were performed in 1856 patients who underwent cytological evaluation and biomolecular analysis. Results: Cytology showed high positive predictive value and specificity for the diagnosis of malignant lesions. BRAF V600E mutation was found in 115 samples, 80 of which were also cytologically diagnosed as papillary thyroid cancer. BRAF mutation analysis significantly enhanced the diagnostic value of cytology, increasing FNAB diagnostic sensitivity for malignant nodules by approximately 28%. Micro PTC (63% of diagnosed papillary thyroid carcinoma) showed a high prevalence of multifocality, extrathyroidal extension, and lymph node metastases, underlining the malignant potential of thyroid microcarcinomas. Each investigated US/clinical characteristic of suspected malignancy correlated with the presence of a thyroid cancer in thyroid nodules with diameter of at least 4 mm. Conclusions: These data indicate that nodules of at least 4 mm may underlie a thyroid cancer independently of US/clinical characteristics of suspected malignancy, suggesting the need to perform FNAB. The diagnostic sensitivity for thyroid cancer is significantly increased by BRAF V600E mutation analysis, indicating that the screening for BRAF mutation in FNAB samples has a relevant diagnostic potential.

scholarly journals Next generation sequencing in patients with nephrolithiasis: how does it perform compared with standard urine and stone cultures?

2021 ◽  
Vol 13 ◽  
pp. 175628722199497
Author(s):  
Charles U. Nottingham ◽  
Mark A. Assmus ◽  
Alexander W. Peters ◽  
Tim Large ◽  
Deepak K. Agarwal ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Predictive Value ◽  
Primary Outcome ◽  
Renal Stone ◽  
Next Generation ◽  
Urinary Tract Stones ◽  
Standard Culture ◽  
Sensitivity Specificity ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background: Our aim was to compare microorganism detection between standard culture (Ctx) and next generation sequencing (NGS) in patients undergoing surgery for nephrolithiasis; we prospectively compared both urine and stone culture results using these two techniques. Methods: We prospectively compared microorganism detection of urine and stone cultures using Ctx versus NGS in patients undergoing surgery for nephrolithiasis. We analyzed preoperative voided urine (Voided) using both Ctx and NGS. Intraoperatively, renal stone (Stone) cultures were analyzed with Ctx and NGS. The primary outcome was concordance in microorganism detection between Voided Ctx and Stone NGS, as well as between Stone Ctx and Stone NGS. Results: We prospectively evaluated 84 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Voided Ctx predicting Stone Ctx were 66.7%, 73.7%, 54.5%, and 82.4%, respectively. Concordance of Voided Ctx microorganisms to Stone microorganisms decreased when NGS was used for the Stone compared with Ctx. The sensitivity, specificity, PPV, and NPV of Voided NGS to predict Stone Ctx microorganisms were 85.2%, 24.6%, 34.8%, and 77.8%, respectively. The concordance of Voided NGS to Stone microorganisms improved when the Stone was analyzed via NGS compared with Ctx. Conclusion: NGS has a higher detection rate of microorganisms than standard culture for both preoperative urine and stone cultures. Voided NGS was the most sensitive in predicting a positive Stone sample, but the specificity and PPV were, overall, low. Further correlation of NGS microorganism detection with patient outcomes will determine which clinical situations may benefit most from NGS versus standard culture in patients with urinary-tract stones.

Sign in / Sign up

Export Citation Format

Share Document