title: Circulating thyrotropin receptor mRNA as a novel marker of thyroid cancer: clinical applications learned from 1758 samples.
abstract: OBJECTIVE
  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 thyrotropin receptor (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 perioperatively 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 and applications for TSHR mRNA were previously defined from 663 samples from patients with normal, benign, and malignant thyroid disease.
  
  
  RESULTS
  In patients with follicular neoplasms or suspicious cytology, preoperative TSHR mRNA >1 ng/μg had 96% predictive value for DTC, whereas 95% of patients with undetectable mRNA and benign thyroid sonography had benign disease. In patients with DTC, elevated TSHR mRNA levels became undetectable in all patients (n = 64) 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, 96% with undetectable TSHR mRNA also had no 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 follicular neoplasms. TSHR mRNA also represents a new blood test to aid assessment of disease status in thyroid cancer follow-up.
authors.affiliation: Department of Endocrine Surgery, Endocrinology and Metabolism Institute, Cleveland Clinic, Main Campus, Cleveland, OH 44195, USA. milasm@ccf.org
authors.forename: Mira
authors.initials: M
authors.lastname: Milas
authors.forename: Joyce
authors.initials: J
authors.lastname: Shin
authors.forename: Manjula
authors.initials: M
authors.lastname: Gupta
authors.forename: Tomislav
authors.initials: T
authors.lastname: Novosel
authors.forename: Christian
authors.initials: C
authors.lastname: Nasr
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brainard
authors.forename: Jamie
authors.initials: J
authors.lastname: Mitchell
authors.forename: Eren
authors.initials: E
authors.lastname: Berber
authors.forename: Allan
authors.initials: A
authors.lastname: Siperstein
mesh_terms: D000465:Algorithms; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000097:blood; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D011989:Receptors, Thyrotropin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000276:immunology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000601:surgery; D014463:Ultrasonography
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013954:Thyroglobulin