Detection of circulating thyroid cells in peripheral blood

Detection of circulating malignant thyroid cells would provide a method to identify postoperative patients at risk for metastatic thyroid cancer. This hypothesis has not been tested because of the limited sensitivity of currently available techniques. Based on the tissue specificity of thyroglobulin gene expression and the sensitivity of the polymerase chain reaction (PCR) analysis, we performed PCR using primers for thyroglobulin on blood samples from patients with thyroid disease in order to detect thyroglobulin RNA transcripts. Postoperative peripheral blood samples from 81 patients, including patients with known metastatic thyroid cancer (4 papillary and 3 follicular cancers), thyroid cancer and no evidence of current metastases (50 papillary, 7 follicular and 4 patients with both papillary and follicular cancers), benign thyroid disease (6 nontoxic nodular goiters), and normal volunteers (7). Reverse transcriptase-PCR was performed on RNA isolated from whole blood, and positive controls employed RNA from thyroid tissue. Thyroglobulin transcripts were detected in patients with metastatic thyroid cancer, patients with thyroid cancer and no current metastasis (although, of these 8 patients, 5 had metastatic lymph nodes which were removed at the time of operation, one had a history of metastatic disease previously treated by surgery, one had a coexisting parathyroid cancer and one had both papillary and follicular cancers), patients with benign thyroid disease and normal volunteers. Identity of amplicons was confirmed by Southern hybridization with a cDNA for thyroglobulin and by sequencing (the latter in a limited number of cases). These data indicate that PCR can be used to detect thyroglobulin mRNA in peripheral blood and suggest that the presence of these transcripts correlates with the existence of extrathyroidal disease.