Expression of transforming growth factor β₁, β₂, and β₃ in multinodular goiters and differentiated thyroid carcinomas: A comparative study

The various isoforms of transforming growth factor-β (TGFβ) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFβ in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFβ expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFβ in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFβ₁, TGFβ₂, and TGFβ₃ in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFβ isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFβ 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. TGFβ-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles TGFβ-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFβ₁, TGFβ₂, and TGFβ₃ isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFβ expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFβ isoforms in tumorigenesis of thyroid cells.