Genetic Testing and Screening in Medullary Thyroid Cancer

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Nearly a quarter of patients with medullary thyroid cancer (MTC) have a hereditary version of the disease that is related to MEN 2A, MEN 2B, or a familial MTC syndrome. Each of these syndromes is associated with a unique mutations in the RET proto-oncogene with a specific phenotype correlation, explains Lori J. Wirth, MD. Outside of the occurrence of MTC, mutations in MEN 2A are associated with pheochromocytoma and hyperparathyroidism and MEN 2B alterations are related to pheochromocytoma, marfanoid habitus, mucosal neuromas, and Hirschsprung’s disease. Identifying a hereditary syndrome allows for intervention before the onset of cancer, adds Wirth.

A majority of individuals with hereditary MTC have a detectable mutations in the RET gene. As such, it may be important to test all patients with MTC for a germline mutation in this gene. This is particularly important since 5% to 8% of patients without a known family history of MTC will test positive for an inherited mutation in RET, explains Steven I. Sherman, MD.

Once a hereditary cancer is identified, it is important to introduce the immediate family to genetic counseling, since the disease is curable if identified early. Genetic counselors have the ability directly contact and educate family members or help the patient with this process, explains R. Michael Tuttle, MD. If hereditary MTC is noted, screening may be performed very early. In many cases, explains Tuttle, patients with familial mutations may undergo thyroidectomy at 4 to 5 years old. Furthermore, he explains, those in the aggressive MEN 2B group may require surgery even earlier.

A germline mutation in RET can be detected by ordering a simple blood test. Once this mutation is detected in a patient, a less expensive test can be utilized to screen family members, notes Steven Sherman.