Analysis of TGF-β and TGF-β-RII in thyroid neoplasms from the United States, Japan, and China

Transforming growth factor-β (TGF-β) has an inhibitory effect on cell proliferation in various cells and tumors, so loss of TGF-β-receptor (TGF- β-R) may lead to increase proliferative activity in these tumors. We compared the expression of TGF-β and TGF-β-RII in a group of thyroid neoplasms from the United States, Japan, and China to determine if there were differences in the expression of this growth factor or its receptors in various tumor types from different countries. A total 108 neoplastic thyroids from the United States, 42 from Japan, and 46 from China were analyzed for TGF-β1, TGF-β3, and TGF-β-RII by in situ hybridization with riboprobes. TGF-β-RII expression was also examined by immunohistochemistry. TGF-β1 mRNA was expressed in all neoplastic thyroids from all three countries except for one anaplastic carcinoma (ACA). TGF-β3 expression was lowest in follicular carcinomas (FCA) from all three countries (30/42; 71%). TGF-β-RII was much lower in FCA from Japan (1/2; 50%) and China (6/11; 55%) compared to cases from the United States (26/29; 90%). TGF-β-RII expression in papillary carcinoma (PCA) was also lower in carcinomas from Japan (21/28; 75%) and China (23/30; 77%) compared to the United States (24/25; 96%). Most ACA from the United States (25/30; 83%) and from China (3/3; 100%) were positive for TGF-β-RII. Immunohistochemical analysis for TGF-β-RII protein expression showed the highest levels in follicular adenomas (FA) (38/38; 100%) with decreased immunoreactivity in FCA (36/42; 86%), PCA (66/83; 80%), and ACA (14/33; 42%). These findings suggest that loss of TGF-β-RII may be important in thyroid tumor progression and that environmental/geographic factors may play a role in the variable expression of TGF-β-RII in thyroid malignancy.