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Detection of Recurrent Thyroid Cancer by Sensitive Nested Reverse Transcription-Polymerase Chain Reaction of Thyroglobulin and Sodium/Iodide Symporter Messenger Ribonucleic Acid Transcripts in Peripheral Blood¹

Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, 04039-032 Sao Paulo, Brazil

Address all correspondence and requests for reprints to: Rui M. B. Maciel, M.D., Ph.D., Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Rua Pedro de Toledo 781, 12th Floor, 04039-032 Sao Paulo, Brazil. E-mail: rmbmaciel-endo{at}pesquisa.epm.br

To investigate whether circulating thyroglobulin (Tg) messenger ribonucleic acid (mRNA) and sodium/iodide symporter (NIS) mRNA transcripts in peripheral blood are valuable in the follow-up of patients with thyroid cancer, we developed highly sensitive nested Tg and NIS mRNA detection assays and compared their accuracy with serum thyroglobulin (sTg) and whole body scan with ¹³¹I during the monitoring of 34 patients with well differentiated thyroid carcinoma who had undergone total thyroidectomy (17 of 34 also submitted to thyroid ablation with radioiodine) and were taking T₄.

Circulating Tg mRNA was found in 13 of 34 patients, 5 of 13 with detectable and 8 of 13 with undetectable sTg. From these 8 patients with undetectable Tg, 6 showed no cervical radioiodine uptake, and 3 presented proven metastatic disease (2 of them positive for antithyroglobulin antibodies). NIS mRNA was detected in 11 of 34 patients, but its measurement did not improve the ability to detect patients with metastases. Overall, identification of metastatic thyroid cancer was better associated with Tg mRNA than with NIS mRNA, sTg, or whole body scan (83% vs. 16.6% vs. 50% vs. 50%; P < 0.001).

These data showed that circulating Tg mRNA is not only a more sensitive marker of residual thyroid tissue or thyroid cancer than sTg, particularly in patients during T₄ therapy and with positive antithyroglobulin antibodies, but also was more sensitive than NIS mRNA in all patients.

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