Expression of TGF-beta1, TbetaRII and Smad4 in colorectal carcinoma.

Background: Many colorectal carcinomas are resistant to the growth inhibitory response of transforming growth factor-beta (TGF-beta) due to alterations of components along the TGF-beta signaling pathway. The aim of this study was to examine the expression of TGF-beta1, TbetaRII and Smad4 in human colorectal carcinoma and their relationships with cancer growth.

Methods: Immunohistochemistry and in situ hybridization were performed in 38 cases of colorectal carcinoma.

Results: Intense signal for TGF-beta1 protein and TGF-beta1 mRNA were found in 71.1% (27/38) and 77.8% (21/27) of colorectal carcinoma, respectively. Intensive TbetaRII mRNA were detected only in 40% (11/27) cancer tissues (p<0.05). 65.8% (25/38) of colorectal carcinoma displayed decreased expression in TbetaRII immunoreactivity staining (p<0.05). Smad4 protein and Smad4 mRNA were reduced in 63.2% (24/38) and 63% (17/27) of tumors, respectively. Smad4 expression was related to tumor differentiation and Duke's stage (p<0.05). Furthermore, TGF-beta1-positive tumors with lymph node metastasis preferentially had significant reduced Smad4 expression (p<0.05).

Conclusions: Down-regulation of TbetaRII as well as the over-expression of TGF-beta1 play a possible role for the escape of colorectal carcinoma from TGF-beta-mediated growth inhibition. Reduced Smad4 is associated with malignancy and progression of colorectal carcinoma.