Circulating Thyrotropin Receptor (TSHR) mRNA as a Novel Marker of Thyroid Cancer: Clinical Applications Learned from 1,758 Samples
*Mira Milas, *Joyce Shin, *Manjula Gupta, *Tomislav Novosel, *Christian Nasr, *Jamie Mitchell, *Eren Berber, Allan Siperstein
Cleveland Clinic, Cleveland, OH
Objectives Since thyroglobulin, no new blood tests for differentiated thyroid cancer (DTC) have been introduced into routine clinical practice. In initial studies, the detection of circulating DTC cells by TSHR mRNA measurement distinguished benign from malignant thyroid diseases. This prospective validation study tests the ability of TSHR mRNA to diagnose DTC preoperatively and to detect cancer recurrence.
Methods TSHR mRNA was measured by quantitative RT-PCR from blood drawn preoperatively in patients undergoing thyroid surgery (n=526), postoperatively in patients undergoing DTC follow-up (n=418) and in patients monitored for known benign disease (n=151). The reference range for TSHR mRNA was previously defined from 663 samples from patients with normal, benign and malignant thyroid disease.
Results In patients with indeterminate or suspicious cytology, preoperative TSHR mRNA >1 ng/ug had 96% predictive value for DTC, whereas no patients with undetectable mRNA and benign thyroid sonography had cancer at operation. In patients with DTC, elevated TSHR mRNA levels became undetectable in all patients (n=45) on the first postoperative day, except in 5 who manifested persistent or recurrent cervical disease within the year. In long-term follow-up of DTC patients with thyroglobulin antibodies, all with undetectable TSHR mRNA also had no radiologic evidence of cancer recurrence.
Conclusions TSHR mRNA provides an additional clinical tool for the evaluation of patients with thyroid nodules. It is particularly useful in guiding appropriate initial surgery for indeterminate thyroid lesions. TSHR mRNA also represents a new blood test to aid assessment of disease status in thyroid cancer follow-up.