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BAG-1 expression in normal and neoplastic endometrium
T Moriyama1, R D Littell, R Debernardo
1Vincent Center for Reproductive Biology, Massachusetts General Hospital Boston, Boston, MA 02114, USA.
Insights
BAG-1 protein is present in endometrial tissue. High-grade endometrial cancers show increased BAG-1 expression, suggesting it may be a prognostic indicator for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gynecologic Pathology
Background:
- The BCL-2-associated athanogene 1 (BAG-1) protein exhibits anti-apoptotic properties and interacts with BCL-2 and steroid receptors.
- Elevated BAG-1 levels are associated with prognosis in breast cancer, but its role in endometrial cancer is not well-defined.
Purpose of the Study:
- To investigate the expression of BAG-1 in normal endometrium, precancerous lesions, and endometrial cancers.
- To determine if BAG-1 expression correlates with tumor grade and steroid receptor status in endometrial cancer.
Main Methods:
- Immunohistochemical analysis of BAG-1 expression in endometrial tissue samples, including proliferative endometrium, secretory endometrium, low-grade neoplastic lesions, and high-grade endometrial adenocarcinomas.
- Western blot analysis to assess BAG-1 levels in endometrial cancer cell lines representing different grades.
Main Results:
- High-grade endometrial cancers demonstrated significantly higher positive staining for both cytoplasmic and nuclear BAG-1 compared to secretory endometrium.
- No significant correlation was found between nuclear BAG-1 expression and estrogen or progesterone receptor status.
- BAG-1 was expressed across all evaluated endometrial cancer cell lines with no significant difference in total BAG-1 levels.
Conclusions:
- BAG-1 is expressed in the human endometrium.
- Increased expression of BAG-1 in high-grade endometrial cancers suggests a potential role as a prognostic biomarker.
Objective:
BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors. High levels of BAG-1 have been implicated as a prognostic indicator in breast cancer. Whether this observation can be generalized to endometrial cancer remains unknown.
Methods:
IRB permission was obtained for use of human discarded tissue. Immunohistochemical analyses were performed on: proliferative endometrium (PEM, 6), secretory endometrium (SEM, 28), "low-grade" neoplastic lesions (complex atypical hyperplasia and grade 1 endometrial adenocarcinomas) (19), and "high-grade" cancers (grade 2 and 3 endometrial adenocarcinomas) (13). The level of total BAG-1 and its isoforms was evaluated by Western blot in lysates from Ishikawa cells (grade 1), MFE 296 cells (grade 2), and SK-UT(2) cells (grade 3).
Results:
The proportion of "high-grade" cancers with positive cytoplasmic staining for BAG-1 was higher than that of secretory endometrium (P = 0.006). Additionally, the proportion of specimens with positive staining for nuclear BAG-1 expression was significantly higher among high-grade carcinoma specimens compared to secretory specimens (P = 0.009). A high proportion (91%) of all specimens were positive for BCL-2, limiting the ability to subcategorize the other variables analyzed. There was no relationship between positive nuclear BAG-1 expression and either estrogen receptor (ER) or progesterone receptor (PR) expression. BAG-1 was expressed in the three cell lines evaluated and total BAG-1 level was not different among the different cell lines.
Conclusion:
BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis.
