Comparison of Metallothionein (MT) and Ki-67 Antigen Expression in Benign and Malignant Thyroid Tumours

Thyroid carcinomas are the most frequently occurring tumours in the endocrine system. Metallothioneins (MT) and Ki-67 proteins are present in intensely proliferating cells, and their expression has been observed in numerous tumours, including thyroid tumours. The purpose of this study was to analyse the relationship between intensity of MT expression and Ki-67 antigen on one hand and histological features of the examined thyroid tumours on the other. The investigated material included 186 archival paraffin blocks with samples of various thyroid tissues, obtained from the Chair and Department of Pathomorphology, Medical University of Wroclaw. In paraffin sections, immunohistochemical reactions were performed with the use of monoclonal anti-MT (I/II) and anti-Ki-67 antibodies. Intensity of MT and Ki-67 antigen expression was evaluated using a light microscope using the semi-quantitative method of Remmele. A significant difference in MT expression was noted between different tumours of the thyroid: the highest expression was detected in follicular carcinoma and the lowest was detected in medullary carcinoma. Expression of MT was also significantly elevated in follicular carcinoma as compared to follicular adenoma. On the other hand, no significant differences were seen between expression of Ki-67 antigen in follicular adenoma and follicular carcinoma. Moreover, these investigations detected no correlation between the expression of MT and Ki-67 antigen in follicular adenoma and follicular carcinoma. In view of the obtained results, the expression of MT can be considered as a potential marker of differentiation between the two types of thyroid tumours, which are otherwise difficult to differentiate. Carcinomas of the endocrine glands and organs are manifested relatively infrequently. Tumours of the thyroid gland are noted most frequently, comprising 1.8% out of 1.28 million new cases of extradermal cancer, which resulted in 0.41% of 555,500 deaths due to these tumours in the United States in 2002 (1). The highly differentiated carcinomas (papillary and follicular carcinomas) develop from cells of thyroid follicles and they develop most frequently in young, while poorly differentiated anaplastic carcinomas are more frequent in people over 60 years of age. The papillary carcinoma accounts for 70-80% of thyroid tumours and is regarded to be the least aggressive form of carcinoma of the thyroid (2). In turn, follicular carcinoma accounts for 5-15% cases of cancer in the thyroid. Due to difficulties encountered in its differentiation from follicular adenoma, a benign lesion, the two types of tumours are described as follicular tumours. Their differentiation can be executed exclusively in the post-surgical preparation, but the lesions cannot be distinguished using a targeted fine-needle aspiration biopsy (3). Other types of thyroid cancer, such as anaplastic carcinoma (5%) and medullary carcinoma (3-5%) are much less frequent and do not pose great difficulties in histopathological diagnosis (3). Metallothioneins (MT) represent a family of low molecular weight proteins which are expressed in many species. They are highly conserved and are manifested in four principal isoforms of variable manifestation in either healthy or neoplastic tissues (4, 5). The polypeptide chain of MT consists of 61 to 68 amino acids (depending on the isoform) of which 30% of the residues involve cysteines. The MT molecule comprises two domains (C-terminal α and N-terminal β), linked with each other by a lysine dimer. The