Related Experiment Video
Updated: Aug 31, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Loss of Smad4 protein expression occurs infrequently in endometrial carcinomas
Fu-Shing Liu1, Jung-Ta Chen, Yeun-Ting Hsieh
1Department of Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan. fsliu@vghtc.vghtc.gov.tw
Abstract:
Smad4 is a member of the Smad proteins, which are needed for mediating signals of transforming growth factor beta from the cell surface to the nucleus. Smad4 is also a tumor suppressor gene for cancers of the pancreas, colon, and lung. The aim of this study was to investigate the expression and prognostic significance of this gene product in endometrial cancer. Immunohistochemical staining for Smad4 was performed on formalin-fixed, paraffin-embedded specimens of endometrial tumors with an anti-Smad4 monoclonal antibody (clone B8): 97 primary endometrial carcinomas, 20 cases of endometrial hyperplasia, and 26 cases of metastases from endometrial carcinoma. The immunoreactivity of each tumor was correlated with the clinical and histopathologic parameters of the patients. Diffusely positive expression of Smad4 protein was detected in all 20 cases of endometrial hyperplasia and in most of the primary and metastatic endometrial cancers. The frequency of positive expression decreased progressively with tumor grade. Clinically, however, it was not associated with tumor progression, nor did it predict patient outcome. Although loss of heterozygosity at chromosome 18q21 (the location of the Smad4 gene) is frequent in endometrial carcinomas, the authors show in this immunohistochemical study that inactivation of this gene occurs infrequently in this tumor.
Insights
Smad4 protein is frequently expressed in endometrial hyperplasia and cancer, but its expression does not predict patient outcomes. This suggests Smad4 gene inactivation is rare in endometrial carcinomas despite frequent LOH.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Smad4 is a key mediator of transforming growth factor beta signaling.
- Smad4 functions as a tumor suppressor gene in various cancers.
- The role of Smad4 in endometrial cancer requires further investigation.
Purpose of the Study:
- To investigate the expression patterns of Smad4 protein in endometrial hyperplasia and endometrial carcinoma.
- To evaluate the prognostic significance of Smad4 expression in endometrial cancer patients.
Main Methods:
- Immunohistochemical staining using an anti-Smad4 monoclonal antibody on formalin-fixed, paraffin-embedded tumor specimens.
- Analysis included primary endometrial carcinomas, endometrial hyperplasia, and metastatic endometrial carcinoma.
- Correlation of Smad4 immunoreactivity with clinical and histopathologic parameters.
Main Results:
- Smad4 protein was diffusely expressed in all endometrial hyperplasia cases.
- Most primary and metastatic endometrial cancers showed positive Smad4 expression.
- Positive Smad4 expression decreased with increasing tumor grade but did not correlate with tumor progression or patient outcome.
Conclusions:
- Smad4 protein is generally expressed in endometrial hyperplasia and carcinoma.
- Loss of Smad4 expression does not appear to be a common mechanism of inactivation in endometrial cancer.
- Smad4 expression status is not a reliable prognostic marker for endometrial cancer.
More Related Videos
Related Concept Videos
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Abnormal Proliferation
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

