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Expression of Thyroglobulin and Calcitonin in Spontaneous Thyroid Gland Tumors in the Han Wistar Rat

¹ GlaxoSmithKline Research and Development, Ware, Hertfordshire, SG12 ODP, United Kingdom
² Center for Toxicology, Department of Pharmacology, School of Pharmacy, University of London, London, WC1E 7HU, United Kingdom

Correspondence: Address correspondence to: Dr. A. M. Pilling, Pathology Department, Huntingdon Life Sciences, Woolley Road, Alconbury, Huntingdon, Cambridgeshire PE28 4HS, UK; e-mail:pillinga{at}ukorg.huntingdon.com

Spontaneous follicular and C-cell tumors of the thyroid gland in the Han Wistar rat were examined using two morphologic procedures. Firstly, in situ hybridization (ISH) was used to localize thyroglobulin (TG) and calcitonin (CT) mRNAs. Secondly, the proteins for these markers were detected using immunohistochemistry (IHC). The aim was to study the morphology of the tumors and to examine the usefulness of TG and CT markers in the differential diagnosis of these lesions. Follicular tumors with cystic, papillary and follicular patterns showed relatively consistent expression of TG mRNA by ISH, thereby confirming the diagnostic value of this technique. However, no staining for TG markers was observed in solid lesions. In general, C-cell tumors comprised well-differentiated cells that continued to express CT mRNA and peptides even after embolic spread and metastasis. Therefore, the performance of either ISH or IHC for CT markers can be used for diagnostic confirmation. Additional features noted in C-cell tumors included the appearance of tumor emboli or metastases in association with small primary lesions (less than 5 average follicular diameters in size) and the presence of eosinophilic (amyloid-like) material showing immunopositivity for CT peptides. Finally, evidence is provided for the sequestration of TG protein by proliferating C-cells.

Key Words: Wistar rat • thyroid • follicular tumors • c-cell tumors • thyroglobulin • calcitonin

Abbreviations: CCA, C-cell adenoma • CCC, C-cell carcinoma • CCH, C-cell hyperplasia • CT, calcitonin • FCA, follicular cell adenoma • FCC, follicular cell carcinoma • FCH, follicular cell hyperplasia • IHC, immunohistochemistry • ISH, in situ hybridization • MTC, medullary thyroid carcinoma • OM, original magnification • TG, thyroglobulin

Toxicologic Pathology, Vol. 35, No. 3, 348-355 (2007)
DOI: 10.1080/01926230701230270


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