- Diagnosis to resolve indeterminate cytology
- Prognosis through Markers of Aggressiveness
- Treatment with Actionable Markers of Malignancy & Therapeutic Response
Thyroid Cancer DiagnosismiRInform Thyroid OverviewMarkersFAQsCollection InstructionsTest ResourcesScientific ResourcesClinical Advisory BoardReferences
The diagnostic dilemma... The challenge in thyroid cancer diagnosis... Palpable thyroid nodules occur in 5-7% of the adult population, but the clinical relevance of thyroid nodules rests with the need to diagnose thyroid cancer which occurs in 5-15% of them. Fine needle aspiration (FNA) is currently the standard preoperative diagnostic procedure used to evaluate thyroid nodules. The evaluation is performed by a pathologist who looks at cells from the nodule under a microscope to determine if the nodule is benign or malignant. However, in 10-40% of the cases, the cytological diagnosis remains indeterminate, due to overlapping cytological features between benign and malignant nodules⁴. The majority of patients who receive an indeterminate FNA diagnosis undergo surgical resection of either all or a portion of their thyroid gland. However, research has shown that up to 85% of these indeterminate nodules are diagnosed as benign upon post-surgical analysis⁴. The American Thyroid Association (ATA) has created guidelines which seek to provide physicians with tools that better discriminate between benign and malignant thyroid nodules to improve preoperative diagnostic accuracy¹. The miRInform Thyroid Panel is composed of thyroid cancer markers which were given a "C" recommendation by the ATA, meaning the recommendation is based on expert opinion.
miRInform Thyroid is a panel of molecular markers which can aid in the diagnosis of thyroid cancer and improve preoperative diagnostic accuracy for patients with indeterminate thyroid nodules¹. In addition, the Panel can aid in the characterization of malignancy. The Panel consists of 17 analytically validated molecular markers and utilizes fine needle aspirate (FNA) specimens, collected in an easy-to-use nucleic acid preservation solution. The miRInform Thyroid Panel is a cutting edge molecular diagnostic tool utilizing DNA and RNA based markers. Multiple peer-reviewed scientific studies have shown that the mutations and genetic rearrangements, assayed by miRInform Thyroid, correlate with malignant thyroid nodules²∙³. Therefore, miRInform Thyroid can aid physicians in diagnosis and patient management decisions¹.
These markers are recommended by the ATA (recommendation rating of "C") to improve preoperative cytological diagnostic accuracy for indeterminate thyroid nodules¹. Additionally, these mutations and translocations are found in up to 80% of papillary (BRAF, RAS, RET/PTC) and 70% of follicular (RAS, PAX8/PPARγ) thyroid cancers based on post-operative histological analysis⁵.
How do I order the miRInform Thyroid Panel? To order the miRInform Thyroid Panel, you first need to contact Asuragen to request a miRInform Thyroid Starter Kit. The Kit consists of test requisition forms and sample collection and transportation supplies, all of which are provided at no charge. Once you receive these supplies, you will need to collect an extra FNA biopsy, express it into the provided preservative solution, complete the requisition form and ship these items to Asuragen via the included pre-paid FedEx shipping label. How do I ship the FNA specimen to Asuragen for miRInform Thyroid testing? Asuragen will provide you with all of the necessary sample collection and shipping materials including preservative vials, biobags, shipping boxes, FedEx clinical packs and pre-paid FedEx shipping labels. What are the sample requirements for the miRInform Thyroid Panel? The miRInform Thyroid Panel requires one dedicated FNA biopsy containing a minimum of 50ng of tissue. What QC procedures are performed prior to testing to determine the quality of specimens? The quality and quantity of the nucleic acids within extracted FNA specimens are assessed by spectrophotometry. If sufficient sample is available, all attempts will be made to provide test results to the physician. If inadequate sample is present, the physician will be contacted for a replacement sample. Can I put more than one FNA in the same vial of preservative? FNAs from the same nodule can be expressed into the same vial of preservation solution. However, FNAs from different nodules need to be expressed into separate vials and the location of each nodule should be labeled on the requisition form and on the vial correspondingly. What is the turnaround time for the miRInform Thyroid Panel? Results for the miRInform Thyroid Panel can be expected within 7-10 days of the day Asuragen receives the sample and completed test requisition form. How long does the provided solution preserve the FNA specimen for miRInform Thyroid testing? The provided preservative solution keeps FNA specimens good for up to six weeks at ambient temperature. What is the sensitivity and specificity of the miRInform Thyroid Panel? The clinical validation of the miRInform Thyroid Panel is ongoing but the test has been analytically validated. Therefore, neither a clinical sensitivity nor specificity can be given at this time. However, the analytical sensitivity and specificity of the assay is 95% and 99% respectively. Why were the markers which make up the miRInform Thyroid Panel selected? The markers which make up the miRInform Thyroid Panel were selected based upon numerous clinical studies and publications for their high correlation with thyroid cancer. Additionally, these markers are recommended in the American Thyroid Association guidelines to aid in the diagnosis of patients with indeterminate thyroid nodules. What does a positive result mean? The miRInform Thyroid Panel has been analytically validated for the detection of the markers contained within the Panel. A positive result is indicative of the fact that at least one of the markers was detected. The clinical validation of the miRInform Thyroid Panel is ongoing and when it is complete, a clinical indication will accompany a positive result. What does a negative result mean? The miRInform Thyroid Panel has been analytically validated for the detection of the markers contained within the Panel. A negative result is indicative of the fact that none of the markers was detected. It is important to note that a negative result does not mean the nodule was benign.
Request a Sample Collection Kit - Download Requisition Form - Download Sample Report - miRInform® Thyroid Brochure - FNA Collection Instructions
Technical InformationSpecimen: FNA biopsy collected in Asuragen's proprietary nucleic acid preservation solution. Volume: One FNA pass. Container: A provided tube containing Asuragen's proprietary nucleic acid preservation solution. Special Instructions: Specimens should be labeled with 2 or more patient identifiers that match the test requisition form, such as patient name, and DOB. Storage & Shipping Instructions: Store at room temperature (15 to 30°C) and ship at ambient temperature using the materials supplied to you by Asuragen. Causes for Rejection: Asuragen cannot accept specimens for testing if: a. Test requisition form is missing, incomplete, incorrectly filled, or illegible. Common errors include missing patient information, missing collection date, mismatched specimen identifiers between patient tube and the information provided on the test requisition form, lack of physician's signature, etc. b. Improper specimen type is submitted for the test requested. c. Specimen shipment guidelines were not followed. d. Specimen vial is leaking or broken.
- ATA Guidelines
- AAES 2012 Poster
- Asuragen White Paper
- 1056 Indeterminate FNA Study...
- Molecular Diagnosis of FNAs...
- Impact of Mutation Detection...
- Molecular Diagnostics of Thyroid...
- BRAF Derived Risk Stratification...
Erik K. Alexander, M.D.Dr. Erik K Alexander, MD is an Associate Professor of Medicine at Harvard Medical School, and a physician at the Brigham & Women's Hospital in the Division of Endocrinology and the Department of Medicine. Dr. Alexander's clinical expertise is in the field of thyroid illness. Dr. Alexander is actively involved in the care of patients with thyroid nodules and thyroid cancer. His home institution is a referral center for thyroid nodule evaluation, where over 1,500 nodule aspirations occur annually. Dr. Alexander's research in this area seeks to answer clinical questions that can be rapidly translated into the care of affected patients. Dr. Alexander also serves as a member of the American Thyroid Association's Guideline Committee for the evaluation and treatment of patients with thyroid nodules and thyroid cancer. Dr. Alexander's second clinical interest surrounds thyroid illness during pregnancy. He oversees a unique clinic focused on patients with such disorders at the Brigham & Women's Hospital. Dr. Alexander presently serves a member of the International Guidelines Committees for the treatment of thyroid illness during pregnancy, for both the Endocrine Society as well as the American Thyroid Association. Separate from his clinic activities, Dr. Alexander serves as the Director of Medical Student Education for the Brigham & Women's Hospital and Harvard Medical School. In this capacity, he oversees all student activities including implementation of the BWH 3rd-year Principal Clinical Experience. Dr. Alexander also serves as the Clerkship Director for the 3rd year Internal Medicine Clerkship, and the 4th year subinternship in Internal Medicine. He is a resident of the Boston area where he lives with his wife and two children.
Thomas Giordano, M.D., Ph.D.Dr. Giordano received his B.A. from Johns Hopkins University in 1983 and earned his M.D. and Ph.D. through a combined program at Rutgers University and UMDNJ - Robert Wood Johnson Medical School. His graduate studies in the department of Microbiology involved regulation of gene expression by phage T3 and T7 RNA polymerases. He completed residency training in Anatomic Pathology at the National Cancer Institute and fellowship training in Oncologic Pathology at Memorial Sloan-Kettering Cancer Center. After AP training, he joined the faculty of the Department of Pathology at the University of Michigan Medical School as Assistant Professor. Dr. Giordano was promoted to Associate Professor in 2001, and Professor in 2008. He also holds a joint appointment in the Metabolism and Endocrinology Division of the Department of Internal Medicine. Dr. Giordano has interest in the molecular biology of endocrine neoplasia and maintains an active translational research program in endocrine and other neoplastic pathology, using contemporary molecular and genomic profiling techniques to address problems in oncologic pathology. He is also Director of the Tissue Core of the Michigan Comprehensive Cancer Center, Director of the Molecular Pathology Research Laboratory in the UM Department of Pathology, Director of the Biosample Core for the Michigan GI Spore, a member of AP Test Committee for the American Board of Pathology, and Co-Chair of the Thyroid Disease Working Group for The Cancer Genome Atlas project of the NCI. Dr. Giordano is board-certified in Anatomic Pathology.
Mark A. Lupo, M.D.Dr. Mark A. Lupo is a board certified Endocrinologist and is the Medical Director of the Thyroid & Endocrine Center of Florida, located in Sarasota, Florida. He received his medical degree and Internal Medicine training from the University of Florida and then completed Endocrinology training through a combined program at the University of California, San Diego and Scripps Clinic. Dr. Lupo is the past president (2008-2009) of the Academy of Clinical Thyroidologists (ACT) and he is the current Secretary through 2012. Dr. Lupo served on the American Thyroid Association (ATA) Clinical Affairs Committee from 2008-2011. He is currently a core faculty and programming committee member for the American Association of Clinical Endocrinologists (AACE) Basic and Advanced Ultrasound and FNA courses. He also serves on the AACE Nuclear Medicine Certifying Board and AACE Cytology Task Force. Dr. Lupo is ECNU certified in neck ultrasound and has an AIUM accredited ultrasound lab as part of his practice. His primary clinical interests are neck ultrasound and ultrasound-guided fine needle aspiration in the management of thyroid nodules and thyroid cancer.
Susan J. Mandel, M.D., M.P.HDr Mandel is Professor of Medicine and Radiology at the Perelman School of Medicine at the University of Pennsylvania, where she also directs the Endocrine fellowship program. She serves as the Associate Chief of the Division of Endocrinology, Diabetes, and Metabolism at the Hospital of the University of Pennsylvania. After graduating from Harvard College, she received her MD from the College of Physicians and Surgeons, Columbia University, where she also completed her internal medicine residency. She received her fellowship training in endocrinology at the Brigham and Women's Hospital. Dr. Mandel is a member of the Endocrine Society, where she currently serves on Council, the American Association of Clinical Endocrinologists, and the American Thyroid Association. Dr. Mandel is the past President of the Association of Program Directors in Endocrinology, Diabetes, and Metabolism. Her research interests include the use of sonography in the evaluation of patients with thyroid nodules and as surveillance for those with thyroid cancer and thyroid disease during pregnancy. She has been invited to lecture both throughout the United States as well as internationally on these topics. Dr. Mandel served on the writing groups for both the American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer and the Endocrine Society Guideline for the Management of Thyroid Disease During Pregnancy. Dr. Mandel directs the Introductory and Advanced Ultrasound Workshops for the Endocrine Society. She has won prestigious awards for her education and clinical research accomplishments including the 2011 Endocrine Society's laureate Distinguished Educator Award and the George Murray Lectureship Award from the British Thyroid Association. She has authored papers in the New England Journal of Medicine, the Annals of Internal Medicine, and JAMA, as well as publications in endocrine and radiology journals. Dr. Mandel received the AACE 2012 H. Jack Baskin, MD Endocrine Teaching Award. The H. Jack Baskin, MD, Endocrine Teaching Award is given annually to an AACE member in good standing who has made a profound impact in teaching fellows-in-training and who is actively involved in teaching either in a university setting or through AACE.
Daniel Ruan, M.D.Daniel Ruan, MD is a surgeon-scientist committed to the development of novel therapies for patients with thyroid and adrenal tumors. In 2007, he completed his General Surgery Residency at the Brigham and Women's Hospital/Harvard Medical School in Boston, MA. Dr. Ruan then completed his Clinical Fellowship in Endocrine and Oncologic Surgery at the University of California San Francisco in 2008. In 2011, Dr. Ruan was awarded the Fish Surgical Scholar Award at Brigham and Women's Hospital as well as the Faculty Award for Harvard Medical Student Teaching. In addition to his translational research activities, Dr. Ruan has participated in several clinical research studies involving the surgical management of thyroid and adrenal disease. Dr. Ruan has also written several textbook chapters, review papers, and editorials regarding the management of patients with thyroid, parathyroid, and adrenal disease. His contributions take three forms: (1) he started a laboratory research program that focuses on novel treatments for endocrine cancers (2) he has made several contributions to clinical and translational endocrine research; and (3) he has taught and mentored students, residents and fellows who are destined to be academic physicians. Dr. Ruan is an Instructor in Surgery at Harvard Medical School and is an Associate Surgeon at Brigham and Women's Hospital in Boston, MA. He is committed to novel surgical approaches for endocrine surgery.
Leonard Wartofsky, M.D., M.P.H., M.A.C.P.Dr. Wartofsky is a Professor of Medicine, Anatomy, Physiology and Genetics at the Uniformed Services University of the Health Sciences in Bethesda, MD., and Professor of Medicine at Georgetown University School of Medicine. He is Chairman of the Department of Medicine at the Washington Hospital Center. He is a graduate of George Washington University and was awarded the Distinguished Alumnus Achievement Award for 2011. He did his postgraduate training in internal medicine at the Barnes Hospital of Washington University in St. Louis and the Albert Einstein Medical Center in New York, and trained in endocrinology with Dr. Sidney Ingbar on the Harvard University Service, Thorndike Memorial Laboratory, at Boston City Hospital. Dr. Wartofsky is a past Secretary of the American Thyroid Association, and past President of both the American Thyroid Association and The Endocrine Society. He is a recipient of the Distinguished Educator Award of the Endocrine Society, and will receive the Robert H. Williams Leadership Award of the Society in June 2012. He is the editor of books on thyroid cancer for both physicians and for patients, and thyroid cancer is his primary clinical focus. He is the author or coauthor of over 350 articles and book chapters in the medical literature, and began a 5 year term as Editor-in-Chief of the Journal of Clinical Endocrinology & Metabolism in January 2010.
- Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.
- Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009;94:2092-8.
- Cantara S, Capezzone M, Marchisotta S, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab 2010;95:1365-9.
- Baloch, Z.W., et al. Diagnostic terminology and morphologic criteria for cytological diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008; 36(6): p. 425-37.
- Kondo, T., S. Ezzat, and S.L. Asa, Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6(4): p. 292-306.