Thyroglobulin

Sources/Clones
Axcel/Accurate (polyclonal, DAK-Tg6), Biodesign (polyclonal, 101, 102, 103, 104), Biogenesis (polyclonal), Biogenex (polyclonal), Caltag Laboratories (14/14), Dako (polyclonal, DAK-Tg6), Chemicon (polyclonal), Fitzgerald (M370108, M310136, M310137, M310138, M310139), Immunotech SA (J7B49, J7C9-3, J7C76-20), Labvision Corp (2H11, 6E1), Novocastra (polyclonal, ID4), Sanbio/Monosan (14/14) and Zymed (polyclonal).

Fixation/Preparation
The antibodies to thyroglobulin are applicable to formalin-fixed paraffin sections, acetone-fixed cryostat sections and fixed-cell smears.

Background
DAK-Tg6 (IgG1, k) and 1D4 (IgG2a) were raised against purified human thyroglobulin. These antibodies react with thyroglobulin (300 kD) in normal, hyperplastic and neoplastic thyroid glands. Circulating iodide, derived from dietary sources and deiodination of thyroid hormones, is selectively trapped by the thyroid gland. Oxidation of iodine to the organic form is then effected by a thyroid peroxidase enzyme (Magnusson et al, 1987), which is sited at the apical border of the follicular cell. This is now recognised as the antigen to thyroid antimicrosomal antibody in autoimmune disease (Portmann et al, 1988). Organic iodide is then incorporated into mono- and diiodotyrosine by binding to tyrosine residues on thyroglobulin stored in colloid. Thyroglobulin contains 140 tyrosine residues but not all of these are iodinated and T4 and T3 synthesis occurs only at specific sites (Dunn et al, 1987). Hormone release is brought about by endocytosis of thyroglobulin at the apical pole of the follicular stem cell, fusion of endocytotic vesicles with lysosomes and release of T3 and T4 by the proteolytic cleavage of thyroglobulin. These hormones are then secreted into the peripheral blood via the basal pole.

Applications
Apart from being immuno-positive in all papillary and follicular carcinomas, thyroglobulin may also be useful in poorly differentiated and anaplastic carcinomas in up to 50% of cases (Wilson et al, 1986; De Micco et al, 1987). Although both latter entities have been shown biochemically to synthesize 19S thyroglobulin, immunohistochemistry often fails to detect thyroglobulin in these tumors (Monaco et al, 1984). H[thle cell tumors also demonstrate immunopositivity with thyroglobulin. The other major role of antibodies to thyroglobulin is in the identification of metastatic thyroid carcinomas. A note of caution is necessary, since thyroglobulin may be demonstrated in medullary carcinoma of the thyroid gland (Wilson et al, 1986). In such instances, attention to morphology as well as application of calcitonin antibodies would be crucial in avoiding an erroneous diagnosis. Antibodies to thyroglobulin do not react with epithelial cells from GIT, pancreas, kidney, lung and breast nor the malignancies that arise in these organs.

Comments
The main role of thyroglobulin antibody lies in the identification of poorly differentiated/anaplastic carcinomas and metastatic thyroid carcinoma. Normal thyroid tissue may be used as positive controls.

References
•De Micco C, Ruf J, Carayon P, Chrestian M-A, Henry J-F, Toga M 1987.

•Imunohistochemical study of thyroglobulin in thyroid carcinomas with monoclonal antibodies. Cancer 59: 471-476.

•Dunn JT, Anderson PC, Fox JW, et al 1987. The sites of thyroid hormone formation in rabbit thyroglobulin. Journal of Biology Chemistry 262: 16948-16952.

•Magnusson RP, Chazenbalk GD, Gestautas J, et al 1987. Molecular cloning of the cDNA for human thyroid peroxidase. Molecular Endocrinology 1: 856-861.

•Monaco F, Carducci C, De Luca M, Andreoli M, Dominici R 1984. Human undifferentiated thyroid carcinoma synthesizes and secretes 19S thyroglobulin. Cancer 54: 79-83.

•Portmann L, Fitch FW, Harvan W, et al 1988. Characterisation of the thyroid microsomal antigen and its relationship to thyroid peroxidase, using monoclonal antibodies. Journal of Clinical Investigation 81: 1217-1224.

•Wilson NW, Pambakian H, Richardson TC, Stokoe MR, Heyderman E 1986. Epithelial markers in thyroid carcinoma: an immunoperoxidase study. Histopathology 10: 815-829.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.