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Expression of Smad4 and TGF-beta2 in colorectal carcinoma
Ch Kouvidou1, C Latoufis, E Lianou
1Departments of Pathology, Elpis Hospital, Athens, Greece. Tsimtsilisy@Unisystems.gr
Background:
TGF-beta, 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-beta2 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-beta2 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-P2 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-beta2 expression and Dukes' stage (p=0.03). A slight tendency for a relationship between Smad4 and TGF-beta2 (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-beta2 overexpression, due to the activation or deregulation of the TGF-fl signalling pathway. Inactivation of the TGF-beta gene occurs at an early stage of colorectal carcinogenesis, while inactivation of Smad4 is probably a late event.
Insights
Smad4 protein expression was retained in poorly differentiated colorectal cancer and may link to TGF-beta2 overexpression. TGF-beta gene inactivation occurs early in colorectal carcinogenesis, while Smad4 inactivation is likely a late event.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Transforming growth factor-beta (TGF-beta) is a key antiproliferative agent involved in suppressing tumorigenicity.
- Smad4, a tumor suppressor gene at 18q21, mediates TGF-beta effects on gene transcription and cell growth.
- Understanding Smad4 and TGF-beta2 expression is crucial for colorectal cancer research.
Purpose of the Study:
- To investigate Smad4 and TGF-beta2 protein expression in colorectal carcinomas.
- To correlate their expression with clinicopathological parameters and patient survival.
Main Methods:
- Immunohistochemistry was used to analyze Smad4 and TGF-beta2 protein expression.
- 49 cases of formalin-fixed paraffin-embedded colon carcinoma tissue were examined.
- Expression levels were compared to colonic mucosa and correlated with tumor grade, Dukes' stage, and survival.
Main Results:
- Smad4 expression was absent or reduced in 55% of colorectal carcinomas.
- TGF-beta2 cytoplasmic staining was observed in all cases, with overexpression in 48.9%.
- Significant correlations were found between Smad4 and tumor grade (p=0.02), and TGF-beta2 and Dukes' stage (p=0.03).
Conclusions:
- Retained Smad4 expression in poorly differentiated carcinoma may be linked to TGF-beta2 overexpression.
- TGF-beta gene inactivation appears to be an early event in colorectal carcinogenesis.
- Smad4 inactivation is suggested to be a late event in colorectal cancer development.
