European Archives of Oto-Rhino-Laryngology

, Volume 275, Issue 6, pp 1375–1384 | Cite as

Molecular markers in well-differentiated thyroid cancer

  • Anil K. D’Cruz
  • Richa Vaish
  • Abhishek Vaidya
  • Iain J. Nixon
  • Michelle D. Williams
  • Vincent Vander Poorten
  • Fernando López
  • Peter Angelos
  • Ashok R. Shaha
  • Avi Khafif
  • Alena Skalova
  • Alessandra Rinaldo
  • Jennifer L. Hunt
  • Alfio Ferlito
Review Article



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.


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.


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.


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.


Thyroid neoplasm/diagnosis Thyroid neoplasm/genetics Carcinoma, papillary Adenocarcinoma, follicular NIFTP miRNA 




Compliance with ethical standards

Conflict of interest

The authors declare that there is no competing interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anil K. D’Cruz
    • 1
  • Richa Vaish
    • 1
  • Abhishek Vaidya
    • 2
    • 3
  • Iain J. Nixon
    • 4
  • Michelle D. Williams
    • 5
  • Vincent Vander Poorten
    • 6
  • Fernando López
    • 7
  • Peter Angelos
    • 8
  • Ashok R. Shaha
    • 9
  • Avi Khafif
    • 10
  • Alena Skalova
    • 11
  • Alessandra Rinaldo
    • 12
  • Jennifer L. Hunt
    • 13
  • Alfio Ferlito
    • 14
  1. 1.Head Neck ServicesTata Memorial HospitalMumbaiIndia
  2. 2.National Cancer InstituteNagpurIndia
  3. 3.NKPSIMSNagpurIndia
  4. 4.Departments of Surgery and Otolaryngology, Head and Neck SurgeryEdinburgh UniversityEdinburghUK
  5. 5.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Otorhinolaryngology-Head and Neck Surgery and Department of Oncology, Section Head and Neck Oncology, University Hospitals LeuvenKU LeuvenLeuvenBelgium
  7. 7.Department of Otolaryngology, Hospital Universitario Central de Asturias, IUOPAUniversity of Oviedo, CIBERONCOviedoSpain
  8. 8.Department of Surgery and Surgical EthicsThe University of Chicago MedicineChicagoUSA
  9. 9.Head and Neck ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  10. 10.Head and Neck Surgery and Oncology Unit, A.R.M. Center for Advanced Otolaryngology Head and Neck SurgeryAssuta Medical CenterTel AvivIsrael
  11. 11.Department of PathologyCharles University, Faculty of Medicine in PlzenPlzenCzech Republic
  12. 12.University of Udine School of MedicinePaduaItaly
  13. 13.Department of PathologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  14. 14.International Head and Neck Scientific GroupPaduaItaly

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