Oncotargets and Therapy Dovepress Dovepress Diagnostic Value of Braf

hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms V600e-mutation analysis in fine-needle aspiration of thyroid nodules: a meta-analysis Abstract: Fine-needle aspiration (FNA) is a reliable method for preoperative diagnosis of thyroid nodules; however, about 10%–40% nodules are classified as indeterminate. The BRAF V600E mutation is the most promising marker for thyroid FNA. This meta-analysis was conducted to investigate the diagnostic value of BRAF V600E analysis in thyroid FNA, especially the indeterminate cases. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, Elsevier, and the Cochrane Library databases for relevant studies prior to June 2015, and a total of 88 studies were ultimately included in this meta-analysis. Compared with FNA cytology, the synergism of BRAF V600E testing increased the diagnostic sensitivity from 81.4% to 87.4% and decreased the false-negative rate from 8% to 5.2%. In the indeterminate group, the mutation rate of BRAF V600E was 23% and varied in different subcategories (43.2% in suspicious for malignant cells [SMC], 13.77% in atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS], and 4.43% in follicular neoplasm/suspicious for follicular neoplasm [FN/SFN]). The sensitivity of BRAF V600E analysis was higher in SMC than that in AUS/FLUS and FN/SFN cases (59.4% vs 40.1% vs 19.5% respectively), while specificity was opposite (86.1% vs 99.5% vs 99.7% respectively). The areas under the summary receiver-operating characteristic curve also confirmed the diagnostic value of BRAF V600E testing in SMC and AUS/FLUS rather than FN/SFN cases. Therefore, BRAF V600E analysis can improve the diagnostic accuracy of thyroid FNA, especially indeterminate cases classified as SMC, and select malignancy to guide the extent of surgery.

[1]  P. Trimboli,et al.  BRAF‐mutated carcinomas among thyroid nodules with prior indeterminate FNA report: a systematic review and meta‐analysis , 2016, Clinical endocrinology.

[2]  C. Ki,et al.  Evaluation of the Real-Q BRAF V600E Detection Assay in Fine-Needle Aspiration Samples of Thyroid Nodules. , 2015, The Journal of molecular diagnostics : JMD.

[3]  R. Paschke,et al.  Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity , 2015, Cancer cytopathology.

[4]  Suk-Kyeong Kim,et al.  RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma , 2015, Clinical endocrinology.

[5]  Kristin M. Post,et al.  Detection of BRAF mutations on direct smears of thyroid fine-needle aspirates through cell transfer technique. , 2015, American journal of clinical pathology.

[6]  R. Paschke,et al.  Molecular testing of thyroid fine-needle aspirations improves presurgical diagnosis and supports the histologic identification of minimally invasive follicular thyroid carcinomas. , 2015, Thyroid : official journal of the American Thyroid Association.

[7]  Kyoungjune Pak,et al.  Prognostic value of genetic mutations in thyroid cancer: a meta-analysis. , 2015, Thyroid : official journal of the American Thyroid Association.

[8]  S. Rorive,et al.  Next‐generation sequencing improves the diagnosis of thyroid FNA specimens with indeterminate cytology , 2015, Histopathology.

[9]  P. Hou,et al.  Assessment of molecular testing in fine-needle aspiration biopsy samples: an experience in a Chinese population. , 2014, Experimental and molecular pathology.

[10]  M. Sidawy,et al.  Correlation of Thyroid Aspirate Molecular Profiles to Respective Cytology and Histology Results: A Single Aspirator's Experience , 2014 .

[11]  P. Grigsby,et al.  Treatment approach, surveillance, and outcome of well-differentiated thyroid cancer in childhood and adolescence. , 2014, Thyroid : official journal of the American Thyroid Association.

[12]  Jae Young Seo,et al.  Can Ultrasound Be as a Surrogate Marker for Diagnosing a Papillary Thyroid Cancer? Comparison with BRAF Mutation Analysis , 2014, Yonsei medical journal.

[13]  Sarah J. Johnson,et al.  Pilot of BRAF mutation analysis in indeterminate, suspicious and malignant thyroid FNA cytology , 2014, Cytopathology : official journal of the British Society for Clinical Cytology.

[14]  T. Xiao,et al.  [Clinical role of BRAF V600E mutation testing in thyroid nodules]. , 2014, Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery.

[15]  S. Glaysher,et al.  BRAF V600 co-testing in thyroid FNA cytology: short-term experience in a large cancer centre in the UK , 2014, Journal of Clinical Pathology.

[16]  S. Filetti,et al.  BRAF mutation assessment in papillary thyroid cancer: are we ready to use it in clinical practice? , 2014, Endocrine.

[17]  P. Trimboli,et al.  Immunohistochemistry for BRAF(V600E) Antibody VE1 Performed in Core Needle Biopsy Samples Identifies Mutated Papillary Thyroid Cancers , 2014, Hormone and Metabolic Research.

[18]  R. Paschke,et al.  Impact of molecular screening for point mutations and rearrangements in routine air-dried fine-needle aspiration samples of thyroid nodules. , 2014, Thyroid : official journal of the American Thyroid Association.

[19]  T. Xiao,et al.  Impact of Molecular Testing in the Diagnosis of Thyroid Fine Needle Aspiration Cytology: Data from Mainland China , 2014, Disease markers.

[20]  Jae Young Seo,et al.  Additional BRAF mutation analysis may have additional diagnostic value in thyroid nodules with “suspicious for malignant” cytology alone even when the nodules do not show suspicious US features , 2014, Endocrine.

[21]  Jing Zhao,et al.  Diagnostic value of B‐RAFV600E in difficult‐to‐diagnose thyroid nodules using fine‐needle aspiration: Systematic review and meta‐analysis , 2014, Diagnostic cytopathology.

[22]  A. Fabozzi,et al.  BRAF Test and Cytological Diagnosis with a Single Fine Needle Cytology Sample , 2013, Acta Cytologica.

[23]  Kyunghwa Han,et al.  Proper Indication of BRAFV600E Mutation Testing in Fine-Needle Aspirates of Thyroid Nodules , 2013, PloS one.

[24]  W. Kim,et al.  BRAF and RAS Mutations in Follicular Variants of Papillary Thyroid Carcinoma , 2013, Endocrine Pathology.

[25]  P. Ladenson,et al.  Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. , 2013, JAMA.

[26]  R. Seethala,et al.  RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers. , 2013, The Journal of clinical endocrinology and metabolism.

[27]  J. Choi,et al.  Application of BRAF, NRAS, KRAS mutations as markers for the detection of papillary thyroid cancer from FNAB specimens by pyrosequencing analysis , 2013, Clinical chemistry and laboratory medicine.

[28]  M. Xing,et al.  Molecular pathogenesis and mechanisms of thyroid cancer , 2013, Nature Reviews Cancer.

[29]  L. Le,et al.  BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. , 2012, Surgery.

[30]  A. Pinchera,et al.  The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. , 2012, The Journal of clinical endocrinology and metabolism.

[31]  Katia Zavaglia,et al.  A molecular computational model improves the preoperative diagnosis of thyroid nodules , 2012, BMC Cancer.

[32]  G. Forti,et al.  A high-resolution melting protocol for rapid and accurate differential diagnosis of thyroid nodules. , 2012, The Journal of molecular diagnostics : JMD.

[33]  Kyunghwa Han,et al.  BRAFV600E mutation testing in fine needle aspirates of thyroid nodules: potential value of real-time PCR. , 2012, Annals of clinical and laboratory science.

[34]  F. Albarel,et al.  From nodule to differentiated thyroid carcinoma: contributions of molecular analysis in 2012. , 2012, Annales d'endocrinologie.

[35]  M. Henry,et al.  Correlation of thyroid nodule fine‐needle aspiration cytology with corresponding histology at Mayo Clinic, 2001–2007: An institutional experience of 1,945 cases , 2012, Diagnostic cytopathology.

[36]  M. Cañadas-Garre,et al.  Reduction of False-Negative Papillary Thyroid Carcinomas by the Routine Analysis of BRAFT1799A Mutation on Fine-Needle Aspiration Biopsy Specimens: A Prospective Study of 814 Thyroid FNAB Patients , 2012, Annals of Surgery.

[37]  J. Krane,et al.  The atypical thyroid fine‐needle aspiration: Past, present, and future , 2012, Cancer cytopathology.

[38]  M. Zatelli,et al.  Role of ultrasonographic/clinical profile, cytology, and BRAF V600E mutation evaluation in thyroid nodule screening for malignancy: a prospective study. , 2012, The Journal of clinical endocrinology and metabolism.

[39]  C. Ki,et al.  Clinical implication of highly sensitive detection of the BRAF V600E mutation in fine-needle aspirations of thyroid nodules: a comparative analysis of three molecular assays in 4585 consecutive cases in a BRAF V600E mutation-prevalent area. , 2012, The Journal of clinical endocrinology and metabolism.

[40]  G. Bevilacqua,et al.  Detection of the BRAF(V600E) mutation in fine needle aspiration cytology of thyroid papillary microcarcinoma cells selected by manual macrodissection: an easy tool to improve the preoperative diagnosis. , 2012, Thyroid : official journal of the American Thyroid Association.

[41]  E. Cho,et al.  Role of BRAFV600E mutation analysis and second cytologic review of fine‐needle aspiration for evaluating thyroid nodule , 2012, Cancer cytopathology.

[42]  C. Wittwer,et al.  Allele-Specific PCR with Competitive Probe Blocking for Sensitive and Specific Detection of BRAF V600E in Thyroid Fine-Needle Aspiration Specimens , 2011, Acta Cytologica.

[43]  Suk-Kyeong Kim,et al.  The BRAFV600E mutation is associated with malignant ultrasonographic features in thyroid nodules , 2011, Clinical endocrinology.

[44]  W. Faquin,et al.  Update in Thyroid Fine Needle Aspiration , 2011, Endocrine pathology.

[45]  Y. Jo,et al.  Pyrosequencing cut‐off value identifying BRAFV600E mutation in fine needle aspiration samples of thyroid nodules , 2011, Clinical endocrinology.

[46]  R. Seethala,et al.  Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. , 2011, The Journal of clinical endocrinology and metabolism.

[47]  Marina N. Nikiforova,et al.  Molecular genetics and diagnosis of thyroid cancer , 2011, Nature Reviews Endocrinology.

[48]  M. Prasad,et al.  Reflex BRAF testing in thyroid fine-needle aspiration biopsy with equivocal and positive interpretation: a prospective study. , 2011, Thyroid : official journal of the American Thyroid Association.

[49]  R. Valcavi,et al.  Is a five‐category reporting scheme for thyroid fine needle aspiration cytology accurate? Experience of over 18 000 FNAs reported at the same institution during 1998–2007 , 2011, Cytopathology : official journal of the British Society for Clinical Cytology.

[50]  Juan Rosai,et al.  A large multicenter correlation study of thyroid nodule cytopathology and histopathology. , 2011, Thyroid : official journal of the American Thyroid Association.

[51]  Eun-Kyung Kim,et al.  Diagnostic Value of BRAFV600E Mutation Analysis of Thyroid Nodules According to Ultrasonographic Features and the Time of Aspiration , 2011, Annals of Surgical Oncology.

[52]  A. Toniato,et al.  BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves preoperative identification of papillary thyroid carcinoma and represents a prognostic factor. A mono-institutional experience , 2011, Clinical chemistry and laboratory medicine.

[53]  W. Kim,et al.  Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status. , 2011, The Journal of clinical endocrinology and metabolism.

[54]  M. Ferreira,et al.  Can We Explain Heterogeneity Among Randomized Clinical Trials of Exercise for Chronic Back Pain? A Meta-Regression Analysis of Randomized Controlled Trials , 2010, Physical Therapy.

[55]  B. Ljung,et al.  Molecular Testing for Somatic Mutations Improves the Accuracy of Thyroid Fine-needle Aspiration Biopsy , 2010, World Journal of Surgery.

[56]  C. Ki,et al.  BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population. , 2010, The Journal of clinical endocrinology and metabolism.

[57]  Matthias M. Weber,et al.  Detection of Papillary Thyroid Carcinoma by Analysis of BRAF and RET/PTC1 Mutations in Fine-needle Aspiration Biopsies of Thyroid Nodules , 2010, World Journal of Surgery.

[58]  L. Morelli,et al.  High Prevalence of B-RAF Mutation in Papillary Carcinoma of the Thyroid in North-East Italy , 2010, International journal of surgical pathology.

[59]  F. Pacini,et al.  Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. , 2010, The Journal of clinical endocrinology and metabolism.

[60]  Yuri E Nikiforov,et al.  Molecular diagnostics and predictors in thyroid cancer. , 2009, Thyroid : official journal of the American Thyroid Association.

[61]  Stephanie L. Lee,et al.  Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. , 2009, Thyroid : official journal of the American Thyroid Association.

[62]  E. Cibas,et al.  The Bethesda System for Reporting Thyroid Cytopathology , 2009, Springer International Publishing.

[63]  J. Choi,et al.  Dual priming oligonucleotide–based multiplex PCR analysis for detection of BRAFV600E mutation in FNAB samples of thyroid nodules in BRAFV600E mutation–prevalent area , 2009, Head & neck.

[64]  A. Pinchera,et al.  A morpho-molecular diagnosis of papillary thyroid carcinoma: BRAF V600E detection as an important tool in preoperative evaluation of fine-needle aspirates. , 2009, Thyroid : official journal of the American Thyroid Association.

[65]  M. Nikiforova,et al.  Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. , 2009, The Journal of clinical endocrinology and metabolism.

[66]  J. Holden,et al.  B-RAF V600E mutational analysis of fine needle aspirates correlates with diagnosis of thyroid nodules , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[67]  Y. Jo,et al.  Diagnostic value of pyrosequencing for the BRAFV600E mutation in ultrasound‐guided fine‐needle aspiration biopsy samples of thyroid incidentalomas , 2009, Clinical endocrinology.

[68]  A. Pinchera,et al.  BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. , 2008, The Journal of clinical endocrinology and metabolism.

[69]  W. Kim,et al.  Pyrosequencing Analysis for Detection of a BRAFV600E Mutation in an FNAB Specimen of Thyroid Nodules , 2008, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[70]  L. Mansi,et al.  P. Perros (ed), British Thyroid Association, Royal College of Physicians. Guidelines for the management of thyroid cancer 2nd edition. Report of the Thyroid Cancer Guidelines Update Group , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[71]  G. Troncone,et al.  Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. , 2007, Endocrine-related cancer.

[72]  M. Xing,et al.  BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. , 2007, Endocrine reviews.

[73]  M. Latteri,et al.  Fine-needle aspiration molecular analysis for the diagnosis of papillary thyroid carcinoma through BRAF V600E mutation and RET/PTC rearrangement. , 2007, Thyroid : official journal of the American Thyroid Association.

[74]  G. Troncone,et al.  Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings , 2007, Clinical endocrinology.

[75]  R. Domingues,et al.  Searching for RET/PTC rearrangements and BRAF V599E mutation in thyroid aspirates might contribute to establish a preoperative diagnosis of papillary thyroid carcinoma , 2005, Cytopathology : official journal of the British Society for Clinical Cytology.

[76]  P. Ladenson,et al.  Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. , 2004, The Journal of clinical endocrinology and metabolism.

[77]  D. Clark,et al.  Mutational Analysis of BRAF in Fine Needle Aspiration Biopsies of the Thyroid: A Potential Application for the Preoperative Assessment of Thyroid Nodules , 2004, Clinical Cancer Research.

[78]  Yuri E Nikiforov,et al.  RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. , 2003, The Journal of clinical endocrinology and metabolism.

[79]  E. Vamvakas,et al.  Meta-analyses of studies of the diagnostic accuracy of laboratory tests: a review of the concepts and methods. , 1998, Archives of pathology & laboratory medicine.

[80]  J. Fagin,et al.  Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[81]  E. Alexander,et al.  Centralized molecular testing for oncogenic gene mutations complements the local cytopathologic diagnosis of thyroid nodules. , 2014, Thyroid : official journal of the American Thyroid Association.

[82]  小島原典子,et al.  診断精度研究のバイアスリスク評価ツールQUADAS－2：a Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies 2 の活用 , 2014 .

[83]  I. Setianingsih,et al.  Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[84]  M. Zeiger,et al.  BRAF V600E Mutation Independently Predicts Central Compartment Lymph Node Metastasis in Patients with Papillary Thyroid Cancer , 2012, Annals of Surgical Oncology.

[85]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.