Anil K D'Cruz1, Richa Vaish2, Abhishek Vaidya3,4, Iain J Nixon5, Michelle D Williams6, Vincent Vander Poorten7, Fernando López8, Peter Angelos9, Ashok R Shaha10, Avi Khafif11, Alena Skalova12, Alessandra Rinaldo13, Jennifer L Hunt14, Alfio Ferlito15. 1. Head Neck Services, Tata Memorial Hospital, Parel, Mumbai, 400012, India. docdcruz@gmail.com. 2. Head Neck Services, Tata Memorial Hospital, Parel, Mumbai, 400012, India. 3. National Cancer Institute, Nagpur, India. 4. NKPSIMS, Nagpur, India. 5. Departments of Surgery and Otolaryngology, Head and Neck Surgery, Edinburgh University, Edinburgh, UK. 6. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 7. Otorhinolaryngology-Head and Neck Surgery and Department of Oncology, Section Head and Neck Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 8. Department of Otolaryngology, Hospital Universitario Central de Asturias, IUOPA, University of Oviedo, CIBERONC, Oviedo, Spain. 9. Department of Surgery and Surgical Ethics, The University of Chicago Medicine, Chicago, IL, USA. 10. Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 11. Head and Neck Surgery and Oncology Unit, A.R.M. Center for Advanced Otolaryngology Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel. 12. Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic. 13. University of Udine School of Medicine, Padua, Italy. 14. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 15. International Head and Neck Scientific Group, Padua, Italy.
Abstract
PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. METHODS: PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. RESULTS: There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. CONCLUSION: The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.
PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. METHODS: PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. RESULTS: There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. CONCLUSION: The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.
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