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Thyrotropin Receptor/Thyroglobulin Messenger Ribonucleic Acid in Peripheral Blood and Fine-Needle Aspiration Cytology: Diagnostic Synergy for Detecting Thyroid Cancer

Departments of Clinical Pathology (R.A., I.W., M.K.G.), Endocrinology, Diabetes and Metabolism (S.S.K.R.), and General Surgery (K.W., A.S., M.M.), The Cleveland Clinic Foundation, Cleveland, Ohio 44195

Address all correspondence and requests for reprints to: Manjula K. Gupta, Ph.D., Department of Clinical Pathology, L-30, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. E-mail: guptam{at}ccf.org.

Abstract

RT-PCR for thyroglobulin (Tg) and TSH receptor (TSHR) mRNA has been used to detect circulating thyroid cancer cells. Little is known, however, regarding the preoperative sensitivity of this test to detect cancer. Seventy-two patients with thyroid disease (36 with malignancy and 36 with benign disease) were evaluated preoperatively. TSHR and Tg mRNA transcripts were detected by RT-PCR assays, previously determined to be specific for cancer cells. There was 100% concordance between TSHR and Tg mRNA RT-PCR results. Of 36 cancer patients, 11 had recurrent disease, and all were positive by RT-PCR. Among 25 patients with no prior thyroid surgery, 18 tested positive preoperatively (sensitivity 72%). Seven of 36 patients with benign disease tested positive (specificity 80%). The overall preoperative diagnostic accuracy was 77%. Preoperative fine-needle aspiration (FNA) biopsy was performed on 46 of 61 patients with no prior thyroid surgery. FNA was diagnostic in 28 (61%) patients. Preoperative cytology was adequate but not diagnostic in 18 (39%) patients. RT-PCR correctly classified 14 of these 18 patients with indeterminate FNA, and the test detected three of four cancer patients as positive (75% sensitive) and 11 of 14 patients (78% specific) with benign disease as negative. The combined diagnostic performance characteristics for RT-PCR and FNA cytology were sensitivity = 95%, specificity = 83%, and diagnostic accuracy = 89%, with positive and negative predictive values of 84 and 95%, respectively. Our results suggest that the molecular detection of circulating thyroid cancer cells by RT-PCR for TSHR/Tg mRNA complements FNA cytology in the preoperative differentiation of benign from malignant thyroid disease and their combined use may save unnecessary surgeries.

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