Transforming growth factor beta receptors and p27(kip) in thyroid carcinoma

Objective: To investigate the role of cell cycle regulators in the pathogen esis of papillary carcinoma of the thyroid. Design: Resistance to transforming growth factor beta-mediated inhibition i s a well-known pathogenic mechanism in epithelial neoplasias. In a retrospe ctive study, the expression of transforming growth factor beta receptors ty pes I and II, cyclin Dl,and the cyclin-dependent inhibitor p27(kip), was an alyzed by immunohistochemistry. Results were interpreted in the context of clinicopathological data. Patient follow-up ranged from I to 18 years, with a mean of 4 years. Materials: Twenty conventional primary papillary carcinomas and their metas tases were selected according to current pathologic criteria. Nonconvention al papillary carcinomas (eg, tall-cell, columnar) were excluded from the an alysis. Results: Cyclin D1 was expressed more intensely in the tumor than in adjace nt nonneoplastic parenchyma. Within a given tumor, however, there was signi ficant heterogeneity in expression intensity and percentage of positive cel ls, particularly in metastases. Type 1 receptors were strongly expressed in 90% of tumors, while 80% of the tumors revealed low to no expression of ty pe II receptors. In 10% of tumors, type I receptors were absent and type II receptors expressed. Simultaneous absence of both receptors was not observ ed. While p27(kip) was strongly expressed in nonneoplastic thyroid, it was not detected in any of the primary tumors or their metastases, Conclusions: The results strongly suggest that functional abnormalities in type II receptors result in increased levels of cyclin D1 and down-regulati on of p27(kip). This would maintain cells in a proliferative state and woul d promote tumor progression.