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Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma
Jiazhong Jiang1, Thomas M Ulbright, Shaobo Zhang
1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Background:
Fas is a Type I membrane receptor of the tumor necrosis factor/nerve growth factor family. On binding to Fas ligand, a Type II transmembrane protein, the Fas/Fas ligand complex, induces apoptosis in target cells. Dysregulation of Fas and Fas ligand expression has been found in some malignant neoplasms.
Methods:
Using immunohistochemical analysis, the authors studied the expression of Fas and Fas ligand in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue from 95 radical prostatectomy specimens.
Results:
The percentage of cells that stained positively with Fas in benign prostate tissue (mean, 2%) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13%; P = 0.0014) and prostatic adenocarcinoma (mean, 31%; P = 0.0001). The staining intensity of Fas was significantly less in benign prostate tissue compared with the staining intensity in PIN and prostatic adenocarcinoma. The percentage of cells that stained positively with Fas ligand in benign prostate tissue (mean, 13%) was statistically significantly lower compared with that in PIN (mean, 47%; P = 0.0001) and in prostatic adenocarcinoma (mean, 53%; P = 0.0001). The staining intensity of Fas ligand was significantly less in benign prostate tissue compared with that in PIN and prostatic adenocarcinoma.
Conclusions:
Data from the current study indicate that Fas/Fas ligand is elevated in prostatic malignancy, suggesting that Fas-mediated apoptosis may be a potential target for therapeutic intervention.
Insights
Fas and Fas ligand expression are elevated in prostate cancer and precancerous lesions compared to normal tissue. This suggests Fas-mediated apoptosis could be a therapeutic target for prostate malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Pathways
Background:
- Fas is a Type I membrane receptor involved in apoptosis.
- Fas ligand is a Type II transmembrane protein that binds Fas to induce cell death.
- Dysregulation of Fas and Fas ligand is implicated in various cancers.
Purpose of the Study:
- To investigate the expression of Fas and Fas ligand in prostate adenocarcinoma.
- To compare Fas and Fas ligand expression in malignant, precancerous, and benign prostate tissues.
Main Methods:
- Immunohistochemical analysis was performed on 95 radical prostatectomy specimens.
- Expression levels of Fas and Fas ligand were quantified in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue.
Main Results:
- Fas and Fas ligand expression (both percentage of positive cells and staining intensity) were significantly lower in benign prostate tissue compared to PIN and prostatic adenocarcinoma.
- Fas expression was 2% in benign tissue, 13% in PIN, and 31% in adenocarcinoma.
- Fas ligand expression was 13% in benign tissue, 47% in PIN, and 53% in adenocarcinoma.
Conclusions:
- Fas/Fas ligand expression is elevated in prostate malignancy.
- Increased Fas/Fas ligand suggests a role in prostate cancer development.
- Fas-mediated apoptosis represents a potential therapeutic target for prostate cancer.
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