Transforming growth factor-beta type II receptors and smad proteins in follicular thyroid tumors

Objective: Resistance to transforming growth factor (TGF)-beta-mediated cel l growth inhibition is a well-known pathogenic mechanism in epithelial neop lasia, TGF-beta signaling requires normal function of downstream mediators such as TGF-beta receptors (T beta Rs) and Smad proteins. The goal of this study is to investigate the expression of components of the TGF-beta signal ing pathway in follicular tumors of the thyroid, Study Design: Twenty folli cular thyroid neoplasms were classified as adenomas (11) or minimally invas ive follicular carcinomas (9) according to current pathological criteria. P rotein expression was evaluated to identify differences between benign and malignant tumors that could be used as an adjunct to histopathological anal ysis. Methods: Paraffin-embedded tissue sections containing tumor and adjac ent nonneoplastic parenchyma were analyzed by immunohistochemistry for the expression of T beta R type II (T beta R-II) and Smad2, Smad4, Smad6, and S mad7, Expression of each protein in the tumor was compared with that of the corresponding adjacent nonneoplastic thyroid parenchyma. Results: T beta R -II expression was lost in 78% of the carcinomas. In the remaining 22%, T b eta R-II was preserved but Smad2 expression was lost, In all conventional a denomas, however, T beta R-II expression was maintained. Furthermore, all t umors with normal expression of all proteins were adenomas, Conclusions: Do wnregulation of T beta R-II is a consistent abnormality in follicular carci nomas and can be used to differentiate minimally invasive carcinomas from a denomas. Also, downregulation of Smad proteins is another mechanism by whic h carcinomas can become independent from TGF-beta-mediated growth inhibitio n.