Papillary Thyroid Cancer Genetics and Special Cases
Important- In papillary thyroid cancer, there is a lot written about the genes that may be abnormal and we have been involved in some of the ground breaking research in this area. Nevertheless, papillary thyroid cancer genetic analysis is rarely indicated in the evaluation of patients with previously untreated papillary thyroid cancers.
Papillary thyroid cancer genetics is some really technical and complicated stuff that rarely will play a role in the evaluation, diagnosis or treatment of papillary thyroid cancer patients unless the cancer has come back or spread to sites outside of the neck (distant sites). Written by Gary L. Clayman, DMD, MD, FACS. Dr. Clayman has also written extensively about Papillary thyroid cancer on the EndocrineWeb site here and in multiple highly reviewed medical publications. See his publications here. This section of papillary thyroid cancer was also edited by Dr. Rashmi Roy. Last updated November 18, 2018.
Papillary thyroid cancer genetics is some really technical and complicated stuff that rarely will play a role in the evaluation, diagnosis or treatment of papillary thyroid cancer patients unless the cancer has come back or spread to sites outside of the neck (distant sites). Written by Gary L. Clayman, DMD, MD, FACS. Dr. Clayman has also written extensively about Papillary thyroid cancer on the EndocrineWeb site here and in multiple highly reviewed medical publications. See his publications here. This section of papillary thyroid cancer was also edited by Dr. Rashmi Roy. Last updated November 18, 2018.
- Those with a family history of papillary thyroid cancer
- A personal or family history of goiters
- A history of radiation therapy to the thyroid area such as for: Bone marrow transplantation Mantle field radiation for lymphoma
- Exposure to high levels of radiation due to nuclear accidents or weapons testing
- Having a personal or family history of congenital syndromes such as Cowden’s syndrome (a disorder characterized by benign tumors of the skin and mucous membranes called hamartomas)
Papillary Thyroid Cancer Known Associated Genetic Mutations
Papillary thyroid cancer genetic abnormalities have largely been well identified following the human genome project and the cancer genome project. (Nikiforova MN, Nikiforov YE. Molecular genetics and the diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011; 7(10):569-580.)
- The two most common abnormalities associated with papillary thyroid cancers are the BRAF mutation and RET/PTC1 rearrangements (more commonly associated with the classical papillary thyroid cancer).
- RET/PTC3 rearrangements also occur but are much less common and associated more commonly with the solid variant of papillary thyroid cancers.
- Papillary thyroid cancer follicular variants more commonly reveal RAS mutations or PAX8/PPAR gamma rearrangements than the other more classic papillary thyroid cancers.
- Aggressive papillary thyroid cancer variants are potentially suggested by mutations of the TERT promoter, p53 or PI3kinase. To date, identifying these mutations does not translate to targetable treatment approaches and should not direct therapy above what is seen under the microscope (pathology) and Xray findings.
Types of Genetic Analysis Tests
Sometimes when a nodule is biopsied as indeterminate, it is not clearly benign or malignant. In these cases, your doctor may send the thyroid nodule cells for genetic testing. There are three commercially available genetic testing companies for thyroid nodules. They are called Veracyte (Afirma), Asuragen, and ThyroSeq. They each have their own strengths and weaknesses.
- The Veracyte/Afirma test has the ability to tell whether the FNA cytology is benign. If this test tells you that the needle biopsy is benign, then the possibility of it actually being cancer is less than 4% (McIver BM, Castro R et al. An Independent Study of a Gene Expression Classifier (Afirma) in the Evaluation of Cytologiocally Indeterminate Thyroid Nodules. The Journal of Clinical Endocrinology & Metabolism, Vol 99, Issue 11, Nov 1 2014, 4069-4077.)
- Both Assurag, ThyroSeq, and ThyraMIR/ ThyGenX look for the genetic abnormalities mentioned above that are known to be associated with thyroid cancers. If these particular genetic changes are found, then a diagnosis of thyroid cancer is much more likely. (Nikiforov YE, Carty SE, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next generation sequencing assay. Cancer 2014; 120(23):3627-34.)
Genetic testing can sometimes lead you to a surgery if a nodule contains one of these specific gene abnormalities. However, genetic testing may not be necessary if surgery is indicated for other reasons. Genetic testing is rarely needed as part of the evaluation in order to perform the correct surgery for each patient.