DETECTION OF CIRCULATING THYROID-CELLS IN PERIPHERAL-BLOOD

Background. Detection of circulating malignant thyroid cells may provi de a method to identify postoperative patients at risk for metastatic thyroid cancer. Methods. On the basis of tissue specificity of thyrogl obulin gene expression and the sensitivity of the reverse transcriptas e-polymerase chain reaction (RT-PCR) analysis, we performed RT-PCR usi ng primers for thyroglobulin on blood samples from patients with thyro id disease to detect thyroglobulin RNA transcripts. Postoperative peri pheral blood samples from 100 patients, including patients with known metastatic thyroid cancer (six papillary and three follicular), thyroi d cancer and no evidence of current metastases (63 papillary, 10 folli cular, and five patients with both papillary and follicular), benign t hyroid disease (six nontoxic, nodular goiters), and normal volunteers (seven). Results. Thyroglobulin transcripts were detected in nine of n ine patients with metastatic thyroid cancer, seven of 78 patients with thyroid cancer and no current metastases (although of these seven pat ients, five had a history of metastatic disease that had been previous ly treated by surgery, one had a coexisting parathyroid cancer, and on e had both papillary and follicular thyroid cancers), zero of six pati ents with benign thyroid disease, and zero of seven normal volunteers. Identity of amplicons was confirmed by restriction enzyme digestion a nd by cloning and sequencing of RT-PCR amplified thyroglobulin fragmen t (the latter in a limited number of cases). Conclusions. These data i ndicate that RT-PCR can be used to detect thyroglobulin mRNA in periph eral blood. The presence of these transcripts correlates with the exis tence of extrathyroidal disease.