Expression of transforming growth factor beta(1), beta(2), and beta(3) in multinodular goiters and differentiated thyroid carcinomas: A comparative study

The various isoforms of transforming growth factor-beta (TGF beta) are grow th-inhibiting cytokines for cells of epithelial origin. In malignant thyroi d tumors, several studies documented a high expression of TGF beta in the m ajority of thyroid follicular cells suggesting a possible role as an inhibi tor of cell proliferation. In contrast to this uniform pattern of TGF beta expression in thyroid cancer, scarce and controversial data have been repor ted on the expression of TGF beta in benign multinodular goiter. In the pre sent study, we therefore analyzed the expression of TGF beta(1), TGF beta(2 ), and TGF beta(3) in normal thyroid tissue, multinodular goiters and papil lary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGF beta isoforms was barely detectable. However, in th e carcinomas, almost all epithelial cells displayed immunoreactivity for th e three TGF beta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGF beta-immunostaining was found in scatte red clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGF beta-positivity was pre sent in spite of immunostaining for proliferating cell nuclear antigen (PCN A), a marker for actively proliferating cells. In conclusion, this study sh ows that thyroid carcinomas and benign tumors express the TGF beta(1), TGF beta(2), and TGF beta(3) isoforms. In contrast to the abundant and homogene ous expression in differentiated thyroid carcinomas, TGF beta expression di splays a highly variable interfollicular and intrafollicular pattern in mul tinodular goiters, suggesting an important role of TGF beta isoforms in tum origenesis of thyroid cells.