ORIGINAL ARTICLE

Measurement of thyroglobulin mRNA in peripheral blood as an adjunctive test for monitoring thyroid cancer

D Grammatopoulos¹, Y Elliott², S C Smith², I Brown³, R J Grieve³, E W Hillhouse¹, M A Levine⁴, M D Ringel⁵

¹ Molecular Medicine Research Centre, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
² Biochemistry Department, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
³ Oncology Department, University Hospitals Coventry and Warwickshire NHS Trust
⁴ Division of Pediatric Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
⁵ Washington Hospital Center and Medstar Research Institute, Washington DC 20010, USA

Correspondence to:
Correspondence to:
Dr D Grammatopoulos, The Sir Quinton Hazell Molecular Medicine Research Centre, Department of Biological Sciences, The University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK;
dgrammatopoulos{at}bio.warwick.ac.uk

Aims: Monitoring treated patients with thyroid cancer for recurrent or metastatic disease is currently based upon the serial measurement of circulating plasma thyroglobulin (Tg) concentrations. However, the clinical usefulness of Tg immunoassays is limited by poor sensitivity and interference from anti-Tg antibodies. This study investigated whether the detection of Tg mRNA in peripheral blood, using reverse transcriptase polymerase chain reaction (RT-PCR), is of value in the biochemical surveillance of patients with thyroid cancer.

Methods: RNA was extracted from peripheral blood of five normal controls, six patients with abnormal thyroid function tests, and 28 patients who had undergone thyroidectomy for well differentiated thyroid cancer. From each, an 87 bp product from base pair 262 to 348 in the cDNA sequence of the thyroglobulin gene was amplified by RT-PCR.

Results: Tg mRNA was detected in normal individuals and patients with thyroid cancer. In the group of patients studied, identification of metastatic thyroid tissue by radioiodine scanning correlated better with Tg mRNA assay results than with serum Tg concentrations (accuracy 84% v 75%). No interference from circulating Tg antibodies was apparent. In patients studied prospectively over a 12 month period, there was a significant correlation between detectable Tg mRNA in peripheral blood and the presence or absence of metastatic disease, as demonstrated by radioiodine scanning.

Conclusions: These results suggest that detection of Tg mRNA in blood is a more sensitive marker for metastatic thyroid disease than Tg immunoassay, and appears to be unaffected by the presence of circulating anti-Tg antibodies.

Keywords: thyroglobulin mRNA; thyroid cancer

Abbreviations: RT-PCR, reverse transcriptase polymerase chain reaction; Tg, thyroglobulin; TSH, thyrotrophin

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