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Metallothionein expression in normal, hyperplastic, and neoplastic thyroid follicular and parafollicular C cells using monoclonal antimetallothionein antibody E9

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Abstract

Metallothioneins (MTs) are a set of ubiquitous low molecular proteins with a high affinity for metal ions, such as zinc, copper, and cadmium. MT overexpression can be induced by these metal ions as well as by other endogenous and exogenous factors. In this study, normal, hyperplastic, and neoplastic thyroid tissues of both follicular and C-cell origin were immuno-histochemically investigated with a monoclonal antibody against I- and II-isoforms of MTs. MT immunoreactivity was demonstrated in the follicular epithelium of 19 normal thyroid glands and in all 32 cases of Graves’ disease investigated; 26 of 30 follicular adenomas and 25 of 28 follicular carcinomas showed MT immunoreactivity, whereas only 7 of 20 papillary carcinomas were MT-positive (p < 0.0001 ). In 3 of the 7 positive samples, positivity was restricted to follicular areas of differentation. No MT could be immunolocalized in normal and hyperplastic C cells and medullary thyroid carcinomas (n = 20). In mixed medullary-follicular carcinomas (n = 4), MT staining patterns resembled those seen for thyroglobulin. In anaplastic carcinomas, MTs were mainly immunolocalized in nonspindle cell areas. MT expression in thyroid tumors may reflect the different biological behavior of follicular and papillary carcinomas. Antibodies to MTs may also serve as fairly specific immunohistochemical markers of follicular cell differentiation in thyroid neoplasia.

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References

  1. Andrews GK, Adamsen ED, Gedamu L. Oncogeny of expression of murine metallothionein: comparison with the alpha-fetoprotein gene. Rev Biol 103:294–303, 1984.

    CAS  Google Scholar 

  2. Andrew SM, Jasani B. An improved method for the inhibition of endogenous peroxidase non-deleterious to lymphocyte surface markers. Application to immunoperoxidase studies on eosinophil-rich tissue preparations. Histochem J 19:426–430, 1987.

    Article  CAS  Google Scholar 

  3. Andrews PA, Murphy MP, Howell SB. Metallothionein-mediated cisplatin resistance in human ovarian carcinoma cells. Cancer Chemother Pharmacol 19:149–154, 1987.

    Article  CAS  Google Scholar 

  4. Banerjee D, Onosaka S, Cherian MG. Imunohistochemical localization of metallothionein in cell nucleus and cytoplasm of rat liver and kidney. Toxicology 24:95–105, 1982.

    Article  CAS  Google Scholar 

  5. Bremner I, Davies NT. The induction of metallothionein in rat liver by zinc injection and restriction of food intake. Biochem J 149:733–738, 1975.

    Article  CAS  Google Scholar 

  6. Cherian MG, Goyer RA. Metallothioneins and their role in the metabolism and toxicity of metals. Life Sci 23:1–8, 1978.

    Article  CAS  Google Scholar 

  7. Cousins RJ. Metallothionein—aspects related to copper and zinc metabolism. J Inher Metab Dis 6:15–21, 1983.

    Article  CAS  Google Scholar 

  8. Douglas-Jones AG, Thomas ND, Elmes ME, Jasani B. Immunocytochemically detectable metallothionein in granulation tissue surrounding mucosal ulceration. Histochem J 24:40–50, 1992.

    Article  CAS  Google Scholar 

  9. Elmes ME, Clarkson JP, Mahy NJ, Jasani B. Metallothionein and copper in liver disease with copper retention—a histopathological study. J Pathol 158:131–137, 1989.

    Article  CAS  Google Scholar 

  10. Evering WE, Haywood S, Elmes ME, Jasani B, Trafford J. Histochemical and immunohistochemical evaluation of copper and metallothionein in the liver and kidney of copper-loaded rats. J Pathol 160:305–312, 1990.

    Article  CAS  Google Scholar 

  11. Fuller CE, Elmes ME, Jasani B. Age-related changes in metallothionein, copper, copper-associated protein, and lipofuscin in human liver: a histochemical and immunohistochemical study. J Pathol 161:167–172, 1991.

    Article  Google Scholar 

  12. Hedinger C, Williams ED, Sobin LH. Histological typing of thyroid of tumours. In: Histological Classification of Tumours. Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong: World Health Organisation, Springer-Verlag, 1988.

    Google Scholar 

  13. Hittmair A, Schmid KW. Inhibition of endogenous peroxidase for the immunohistochemical demonstration of intermediate filament proteins (IFP). Immunol Methods 116:199–205, 1989.

    Article  CAS  Google Scholar 

  14. Jasani B, Elmes ME. Immunohistochemical detection of metallothionein. Methods Enzymol 205:95–107, 1991.

    Article  CAS  Google Scholar 

  15. Kägi JHR, Himmelhoch SR, Whanger PD, Bethune JL, Vallee BL. Equine hepatic and renal metallothioneins: purification, molecular weight, amino acid composition, and metal content. J Biol Chem 249:3537–3542, 1974.

    PubMed  Google Scholar 

  16. Kägi JHR, Nordberg M. Metallothionein. Basel: Birkhauser Verlag, 48–116, 1979.

    Book  Google Scholar 

  17. Karasawa M, Hosoi J, Hashiba H, Nose K, Tohyama C, Abe E, Suda T, Kuroki T. Regulation of metallothionein gene expression by 1-alpha, 25-dihydroxy vitamin D3 in cultured cells and in mice. Proc Natl Acad Sci USA 84:8810–8814, 1987.

    Article  CAS  Google Scholar 

  18. Kelley SM, Basu A, Teicher BA, Hacker MP, Hamer DH, Lazo JS. Overexpression of metallotheionein confers resistance to anticancer drugs. Science 241:1813–1815, 1988.

    Article  CAS  Google Scholar 

  19. Klaassen CD. Induction of metallothionein by adrenocortical steroids. Toxicology 20: 275–279, 1981.

    Article  CAS  Google Scholar 

  20. Kontozoglou TE, Banerjee D, Cherian MG. Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch [A] 415:545–549, 1989.

    Article  CAS  Google Scholar 

  21. Nartey N, Cherian MG, Banerjee D. Immunohistochemical localization of metallothionein in human thyroid tumors. Am J Pathol 129:177–182, 1987.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Oh SH, Deagen JT, Whanger PD, Weswig PH. Biological functions of metallothionein: its induction in rats by various stresses. Am J Physiol 234:282–285, 1978.

    Google Scholar 

  23. Onosaka S, Cherian GM. The induced synthesis of metallothioneins in various tissues of rat in response to metals I. Effect of repeated injection of cadmium salts. Toxicology 22:91–101, 1981.

    Article  CAS  Google Scholar 

  24. Reid A, Pereira H, Galea M, Bell JA, Elston CW, Jasani B, Schmid KW, Kay J, Cryer A, Blarney RW, Ellis IO. Metallothionein in human breast cancer. J Pathol 167 (suppl): 29A, 1992.

    Google Scholar 

  25. Riordan JR, Richards V. Human fetal liver contains both zinc and copper-rich forms of metallothionein. J Biol Chem 255:5380–5384, 1980.

    PubMed  CAS  Google Scholar 

  26. Ryden L, Deutsch HF. Preparation and properties of the major copper-binding component in human fetal liver. J Biol Chem 253:519–524, 1978.

    PubMed  CAS  Google Scholar 

  27. Schmid KW, Ellis IO, Gee JMW, Darke B.M, Lees WE, Kay J, Cryer A, Stark JM, Hittmair A, Öfner D, Dünser M, Margreiter R, Daxenbichler G, Nicholson RI, Bier B, Böcker W, Jasani B. Presence and possible significance of immunocytochemically demonstrable metallothionein overexpression in primary ductal carcinoma of the breast. Virchows Arch [A] 422:153–159, 1993.

    Article  CAS  Google Scholar 

  28. Schmid KW, Hittmair A, Tauscher T, Dünser M, Tötsch M, Öfner D, Jasani B. Metallothionein-expression in Mammakar-zinomen—Zusammenhang mit Zytostati-karesistenz, Östrogenrezeptorstatus und Prognose. Verh Dtsch Ges Pathol 74:598, 1990.

    Google Scholar 

  29. Shukla VK, Laidler P, Schmid KW, Zeiger B, Horgan K, Hughes LE, Elmes ME, Jasani B. Metallothionein as a discriminant marker in thin melanoma. J Pathol 169: 177A, 1993.

    Google Scholar 

  30. Slater EP, Cato ACB, Karin M, Baxter JD, Beato M. Progesterone induction of metallothionein-IIA gene expression. Mol Endocrinol 2:485–491, 1988.

    Article  CAS  Google Scholar 

  31. Thomalley PJ, Vasak M. Possible role of metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with Superoxide and hydroxyl radicals. Biochem Biophys Acta 827:36–44, 1985.

    Google Scholar 

  32. Webb M, Cain K. Functions of metallothionein. Biochem Pharmacol 31:137–142,1982.

    Article  CAS  Google Scholar 

  33. Webber MM, Rehman SMM, James GT. Metallothionein induction and deinduction in human prostatic carcinoma cells: relationship with resistance and sensitivity to adriamycin. Cancer Res 48:4503, 1988.

    PubMed  CAS  Google Scholar 

  34. Zeiger B, Hittmair A, Schir M, Öfner C, Öfner D, Fritsch PO, Böcker W, Jasani B, Schmid KW. Immunohistochemically demonstrated metallothionein expression in malignant melanoma. Histopathology 23:257–264, 1993.

    Article  Google Scholar 

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Schmid, K.W., Greeff, M., Hittmair, A. et al. Metallothionein expression in normal, hyperplastic, and neoplastic thyroid follicular and parafollicular C cells using monoclonal antimetallothionein antibody E9. Endocr Pathol 5, 114–122 (1994). https://doi.org/10.1007/BF02921379

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