Contemporary Challenges in the Management of Thyroid Cancer
May 2011
Volume 2, Issue 1

Summary statement: Utility of molecular marker testing in thyroid cancer

Surgery. 2010;148(6):1313-5

Currently, there is ongoing research into the use of molecular markers for thyroid cancer diagnosis, prognosis, and surveillance.  This research could lead to improvements in fine needle aspiration biopsy (FNAB) as a diagnostic tool to predict malignancy.  The molecular marker research could also lead to more accurate prognostic information both preoperatively and postoperatively.

Diagnosis
Several promising studies have been done that suggest that molecular markers can potentially improve the diagnostic accuracy of FNAB.  Since 20 to 30% of FNAB cytology results are indeterminate—therefore requiring operative resection for a diagnosis—increasing the diagnostic accuracy of FNAB would be beneficial. A number of pathology laboratories nationally can do this by detecting gene mutations in the FNAB specimen that are present only if there is thyroid cancer (for example, BRAF mutation). Using a blood test TSHR mRNA is another method to identify which patients with indeterminate FNAB may be at higher risk for thyroid cancer.

Prognosis
Researchers are getting a better understanding of the molecular alterations in thyroid cancer.  As they grow in their ability to identify these alterations, they gain more information on the genotype-phenotype association and prognosis.

For example, in follicular carcinoma, researchers know that long-term survival in certain patients can be correlated with fractional allelic loss in a panel of tumor suppressor genes.

As another example, mutations in the BRAF gene, such as V600E, are associated with papillary thyroid carcinoma (PTC).  In most retrospective studies, BRAF mutations correlate with histopathologic findings of aggressive disease.  Other studies have shown that patients with BRAFV600E-positive PTC are more likely to have the thyroid cancer recur and have decreased disease-specific survival.  Additionally, reoperation is more likely for those patients who have BRAFV600E-positive PTC.

Surveillance
Detecting TSHR mRNA in peripheral blood may be an additional postoperative indicator of persistant (or recurrent) thyroid cancer.

At this moment, measuring serum thyroglobulin (Tg) levels is the only blood test for seeing how patients are doing in long-term follow-up for thyroid cancer.  However, it is unreliable in 20% to 30% of patients because of Tg antibodies.

Therefore, using TSHR mRNA tests may be helpful.  In one study, 119 patients with Tg antibodies or uninterpretable Tg levels after subtotal thyroidectomy were tested for TSHR mRNA.  Undetectable TSHR mRNA levels were correlated with disease-free status with 96% specificity and 100% negative predictive value.

Also, other researchers have detected BRAF mutations in peripheral blood samples from patients with metastatic or residual PTC.

Conclusion
Using molecular markers has great potential in thyroid cancer.  Similar markers are already being used to optimize surgical and medical treatment in many areas of oncology. Applications for thyroid cancer include being able to choose which extent of thyroid surgery a patient should have first (total thyroidectomy or only lobectomy), and being better able to diagnose thyroid cancer initially and during long-term surveillance.

Commentary

The summary statement by Yip et al was based on a symposium at the American Association of Endocrine Surgeons 2010 annual meeting that was devoted to molecular markers in thyroid cancer. It highlighted the strategies in molecular medicine that have been investigated thus far for thyroid cancer management, and which may already be available for patient care. The next 5-10 years will likely witness incorporation of a number of molecular markers into daily decision-making for patients with thyroid nodules, thyroid cancer, and those needing thyroid surgery. The above review is not intended to be comprehensive. Other investigators continue to contribute new molecular tools for application to thyroid diseases (Chudova et al, J Clin Endocrinol Metab. 2010 Dec;95(12):5296-304). The above review, however, is concise, up-to-date and recommended for familiarization with diagnostic tools that may gain more widespread use in the near future. 

Next Article:
Familial Syndromes Associated with Thyroid Cancer in the Era of Personalized Medicine
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