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The role of bcl-2 expression in breast carcinomas (Review)
G J Zhang1, I Kimijima, A Tsuchiya
1Department of Surgery II, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Abstract:
The proto-oncogene bcl-2 is demonstrated to block a final common pathway leading to apoptosis and is expressed in more than half of human breast cancers. Invasive breast cancer has reduced bcl-2 immunostaining compared with normal breast epithelia and preinvasive breast lesions. As an inhibitor of apoptosis, bcl-2 should correlate with highly aggressive tumor biology and resistance to hormonal/cytotoxic therapy. However, high bcl-2 expression has been shown to associate with a number of favorable prognostic factors including ER positivity, PgR positivity, low histological grade, well-differentiated tumor, absence of c-erbB-2 and p53. Unexpectedly, numerous studies have shown that tumors with high bcl-2 expression are more responsive to hormone therapy and have more favorable disease-free and overall survival. The clinical significance of bcl-2 in tumorigenesis and prognosis of breast carcinomas from the data recently published are reviewed. Its role in modulation of hormonal/cytotoxic therapy and future directions are also discussed.
Insights
The proto-oncogene bcl-2 inhibits apoptosis and is found in many breast cancers. Despite expectations, high bcl-2 expression correlates with better prognosis and treatment response in breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The proto-oncogene bcl-2 plays a crucial role in blocking apoptosis.
- bcl-2 is expressed in over 50% of human breast cancers.
- Reduced bcl-2 immunostaining is observed in invasive breast cancer compared to normal or preinvasive lesions.
Purpose of the Study:
- To review the clinical significance of bcl-2 in breast cancer tumorigenesis and prognosis.
- To discuss the role of bcl-2 in modulating hormonal and cytotoxic therapies.
- To explore future research directions regarding bcl-2 in breast cancer.
Main Methods:
- Review of recently published data on bcl-2 in breast carcinomas.
- Analysis of bcl-2 expression in relation to prognostic factors.
- Evaluation of bcl-2's impact on therapeutic responses.
Main Results:
- High bcl-2 expression is unexpectedly associated with favorable prognostic factors (e.g., ER/PgR positivity, low grade).
- Tumors with high bcl-2 expression demonstrate increased responsiveness to hormone therapy.
- High bcl-2 expression correlates with improved disease-free and overall survival.
Conclusions:
- The clinical significance of bcl-2 in breast cancer prognosis is complex and counterintuitive.
- bcl-2 expression levels can predict treatment response and patient survival outcomes.
- Further research is warranted to fully elucidate bcl-2's role in breast cancer therapy and progression.