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Expression of transforming growth factor beta1, beta2, and beta3 in multinodular goiters and differentiated thyroid
E T Kimura1, P Kopp, J Zbaeren
1Laboratory of Experimental Endocrinology, Inselspital, Bern, Switzerland. etkimura@usp.br
Abstract:
The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta 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. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-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 TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.
Insights
Transforming growth factor-beta (TGFbeta) isoforms are expressed in thyroid tumors. While consistently high in carcinomas, expression is variable in benign goiters, suggesting a role in thyroid tumorigenesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Transforming growth factor-beta (TGFbeta) isoforms are growth-inhibiting cytokines for epithelial cells.
- High TGFbeta expression is documented in malignant thyroid tumors, suggesting a role in inhibiting cell proliferation.
- Data on TGFbeta expression in benign multinodular goiter is scarce and controversial.
Purpose of the Study:
- To analyze the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters, and papillary thyroid carcinomas.
- To compare TGFbeta expression patterns between normal tissue, benign goiters, and malignant tumors.
- To investigate the potential role of TGFbeta isoforms in thyroid tumorigenesis.
Main Methods:
- Immunohistochemistry was used to detect TGFbeta1, TGFbeta2, and TGFbeta3 expression.
- Analysis included normal thyroid tissue, benign multinodular goiters, and papillary thyroid carcinomas.
- Proliferating cell nuclear antigen (PCNA) was used as a proliferation marker.
Main Results:
- TGFbeta isoforms were barely detectable in normal thyroid tissue.
- Papillary thyroid carcinomas showed high and homogeneous immunoreactivity for all three TGFbeta isoforms in almost all epithelial cells.
- Multinodular goiters exhibited variable and heterogeneous TGFbeta expression patterns within and among follicles, even in the presence of PCNA.
Conclusions:
- Thyroid carcinomas and benign tumors express TGFbeta1, TGFbeta2, and TGFbeta3 isoforms.
- Differentiated thyroid carcinomas exhibit abundant and homogeneous TGFbeta expression.
- The variable TGFbeta expression in multinodular goiters suggests a significant role in thyroid cell tumorigenesis.