Exp Clin Endocrinol Diabetes 2014; 122 - P082
DOI: 10.1055/s-0034-1372099

MCT 8 and LAT 2 expression in differentially functioning benign and malignant thyroid tumors

S Ting 1, V Tiedje 2, J Badziong 2, O Selich 2, SY Sheu 1, LC Moeller 2, J Weber 3, KW Schmid 1, K Brix 3, D Führer 2, D Zwanziger 2
  • 1University Duisburg-Essen, Institute of Pathology, Essen, Germany
  • 2University Duisburg-Essen, Clinic for Endocrinology, Essen, Germany
  • 3Jacobs University Bremen, Research Center MOLIFE – Molecular Life Science, Bremen, Germany

Introduction: Monocarboxylate transporter 8 (MCT8) and the L-type-amino acid transporter 2 (LAT2) are thyroid hormone (TH) transporters, located in several organs including the thyroid gland. While MCT8 functions as a specific TH transporter, LAT2 also transports other substrates. We asked whether alterations of MCT8 and LAT2 expression occur in thyroid tumors showing distinct biological properties.

Methods: MCT8 and LAT2 expression were evaluated by immunohistochemistry in 200 thyroid tumor samples of follicular adenoma (FA), follicular thyroid carcinoma (FTC), papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid cancer (ATC). Tumor staining intensity was graded by calculating the 'hybrid' (H) score. In addition, mRNA expression was determined in 80 hyper- and hypofunctional nodules, thyroid cancer and normal thyroid tissues. Moreover, expression of MCT8 and LAT2 were investigated by RT-PCR and Western blotting in the human nthy-ori cell line and different human thyroid cancer cell lines (B-CPAP, BHT-101, C-643, FTC-133, -236, -238, K1, TPC-1).

Results: MCT 8 protein was expressed in FA: 30/42 samples (median H-score: 58); FTC: 26/44 (36); PTC: 21/37 (34); PDTC: 15/37 (50) and ATC: 4/35 (4).. LAT 2 protein was expressed in FA: 42/44 samples (75); FTC: 44/45 (73); PTC: 37/39 (101); PDTC: 40/40 (87) and ATC: 32/40 (39). Strong upregulation of MCT8 and LAT2 mRNA was found in toxic adenoma compared to normal thyroid tissue and thyroid carcinomas. MCT8 and LAT2 protein expression was increased in thyroid cancer cell lines versus nthy-ori cells.

Conclusion: Upregulation of MCT8 and LAT2 in toxic adenoma is consistent with involvement of TH transporters in increased TH release during thyrotoxicosis. Partially altered TH transporter expression was observed in thyroid carcinomas, whereby LAT2 expression may be linked with other LAT2 transporter properties involving e.g. amino acid transport rather than TH efflux.