Expression of Smad4 and TGF-β2 in Colorectal Carcinoma

Abstract

Background: TGF-β, a potent natural antiproliferative agent, is believed to play an important role in suppressing tumorigenicity. This effect is mediated through Smad4, a tumour-suppressor gene, at chromosome 18q21, which affects gene transcription and controls cell growth. The aim of the study was to investigate the expression of Smad4 and TGF-β2 in colorectal carcinomas and to correlate them with pathological parameters and patient survival. Materials and Methods: Formalin-fixed paraffin-embedded tissue from 49 cases of colon carcinoma was stained by immunohistochemistry for TGF-β2 and Smad4 protein. Results: Smad4 nuclear and cytoplasmic staining was absent in 9/49 (18.3%) or reduced in 18/49 (36.7%) colorectal carcinoma, while in the remaining 22 (44.8%) Smad4 expression comparable with colonic mucosa was observed. TGF-β2 cytoplasmic staining was expressed in all cases and was overexpressed in 24/49 (48.9%) carcinoma. A statistically significant correlation was found between Smad4 expression and tumour grade (p=0.02) and between TGF-β2 expression and Dukes' stage (p=0.03). A slight tendency for a relationship between Smad4 and TGF-β2 (p=0.25) was also observed. No statistically significant relationship between the above markers and survival was detected. Conclusion: In poorly-differentiated carcinoma, Smad4 protein expression was retained and may be linked to TGF-β2 overexpression, due to the activation or deregulation of the TGF-β signalling pathway. Inactivation of the TGF-β gene occurs at an early stage of colorectal carcinogenesis, while inactivation of Smad4 is probably a late event.