title: Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.
abstract: BACKGROUND
  Thyroid cancer cells express TSH receptor (TSHR) mRNA, and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC).
  
  
  OBJECTIVE
  Our objective was to assess the diagnostic value of circulating TSHR mRNA for preoperative detection of DTC in patients with thyroid nodules.
  
  
  METHODS
  We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery. Eighty-nine patients also had d-1 postoperative levels assessed.
  
  
  METHODS
  TSHR mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or whole-body 131I scans postoperatively.
  
  
  RESULTS
  Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P < 0.0001). At a cutoff value of 1.02 ng/microg total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Of 131 patients with FNA and surgery, 51 were FNA positive (all cancer), 17 were FNA negative (15 benign, two cancer), and 63 were indeterminate. TSHR mRNA correctly diagnosed DTC in 16 of 24 (67%) and benign disease in 29 of 39 (74%) patients with indeterminate FNA (combined sensitivity = 90%; specificity = 80%). Combining TSHR mRNA and ultrasound features for follicular lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short life in circulation, and normalized levels on postoperative d 1 correlated with disease-free status, whereas elevated levels predicted residual/metastatic disease.
  
  
  CONCLUSIONS
  TSHR mRNA measured with FNA enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.
authors.affiliation: Department of Endocrinology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Su-Ynn
authors.initials: SY
authors.lastname: Chia
authors.forename: Mira
authors.initials: M
authors.lastname: Milas
authors.forename: Sethu K
authors.initials: SK
authors.lastname: Reddy
authors.forename: Allan
authors.initials: A
authors.lastname: Siperstein
authors.forename: Mario
authors.initials: M
authors.lastname: Skugor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brainard
authors.forename: Manjula K
authors.initials: MK
authors.lastname: Gupta
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D044963:Biopsy, Fine-Needle; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D011300:Preoperative Care; D012333:RNA, Messenger / Q000097:blood; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000235:genetics*; D012680:Sensitivity and Specificity; D013954:Thyroglobulin / Q000276:immunology; D013964:Thyroid Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D016606:Thyroid Nodule / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D051598:Whole Body Imaging
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013954:Thyroglobulin