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

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.

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

“…All the values are significantly higher than the results obtained from FNA cytologic diagnosis alone. 43 However, owing to the labile nature of RNA in a blood test, TSHR mRNA measurement should be always used and interpreted in view of the clinical context, radiographic findings, and FNA cytologic diagnosis. In addition to the above common somatic mutations and gene arrangement in thyroid cancer, certain miRNA expression levels have been reported to be altered in benign and malignant thyroid lesions.…”

Recent developments in predicting thyroid malignancy

“…Recent investigations have employed reverse transcriptase polymerase chain reaction (RT-PCR) strategies to detect thyroid-specific transcripts as markers of circulating thyroid cancer cells in peripheral blood [41,42]. Examining 72 patients who underwent thyroidectomy, Wagner and colleagues [42] were able to show recently that preoperative measurement of thyroglobulin (Tg) and TSH receptor (TSHR) mRNA in peripheral blood samples by RT-PCR techniques complemented FNAB in differentiating benign and malignant thyroid disease, with sensitivity and specificity of 95 and 83%, respectively.…”

“…Examining 72 patients who underwent thyroidectomy, Wagner and colleagues [42] were able to show recently that preoperative measurement of thyroglobulin (Tg) and TSH receptor (TSHR) mRNA in peripheral blood samples by RT-PCR techniques complemented FNAB in differentiating benign and malignant thyroid disease, with sensitivity and specificity of 95 and 83%, respectively. From a cohort of indeterminate FNA biopsies (n ¼ 18), they were able to detect cancer in three of the four patients with cancer on final pathology [42]. Subsequent and larger studies by the same group examining more specifically TSHR mRNA in peripheral blood samples have shown the modality to improve significantly the specificity for malignancy in FNAB of indeterminate cytology [43,44].…”

Peripheral thyrotropin receptor mRNA as a novel marker for differentiated thyroid cancer diagnosis and surveillance

“…In part to avoid the controversy around Tg mRNA and in part because of excellent initial results with TSHR mRNA, continued studies from Gupta and colleagues have focused on the TSHR mRNA as the principal circulating molecular marker for thyroid cancer [3,8,20,[23][24][25]. Encouragement for this approach began with the studies of Chinnappa et al, who first Review Barbosa & Milas reported a high sensitivity (100%) and specificity (98%) of TSHR mRNA to detect recurrent and residual thyroid cancer, but perhaps even more importantly, found a 95% concordance in this data among Tg mRNA and TSHR mRNA [24].…”

“…TSHR mRNA Peripheral blood analysis [3,6,19,[23][24][25][26][27] Tg mRNA Peripheral blood analysis [11,19,[24][25][26][27] Galectin-3 Microarray-based study and immunostain on specimen [28][29][30][31][32][33][34] HBME-1 Microarray-based study and immunostain on specimen [28,31,32] RET Immunostain, FISH on specimen [32,35] Telomerase Immunostain on FNAB [36] CITED-1 Immunostain on specimen [31] Cytokeratin-19 Immunostain on specimen [31,34] DNA methylation Immunostain on specimen [37] Fibronectin-1 Immunostain on specimen [31,34] CD44V6 Immunostain on specimen [33,38] CD57, p53 Immunostain on specimen [38] Duox Immunostain on specimen [39] Thyoperoxidase Immunostain on specimen [39] DPP IV Histochemistry/enzymatic reaction FNAB [40] PTEN Mutation analysis in Cowden syndrome [41] BRAF Mutation analysis, PCR on specimen [35] ECM-1 cDNA array analysis on specimen [42] TSRP SS4 cDNA array analysis on specimen [42] Molecular profiling Microarray-based study …”