Bcl-2 Expression in Breast Cancer: A Comparative Study at the mRNA and Protein Level

Background: Bcl-2 is one of the most important antiapoptotic genes. Although it facilitates the survival of tumor cells, its expression has been consistently associated with a better prognosis for breast cancer. Virtually all studies on Bcl-2 conducted in breast cancer have been carried out by means of immunohistochemistry. The aim of this study was to examine for the first time the expression of Bcl-2 in a series of human breast cancer, both at the mRNA and protein level. Materials and Methods: One hundred samples from previously untreated human breast cancers were used; Bcl-2 expression was determined both by means of immunohistochemistry using the bcl-2/100/D5 monoclonal antibody and differential RT-PCR. Additionally, the expression of hormone receptors (ER and PR), c-erb-B2, p53 and the proliferation-associated Ki-67 antigen were also studied by means of immunohistochemistry as part of the standard pathological workup. Results: Any degree of immunohistochemical staining correlated significantly and inversely with c-erb-B2 expression (p=0.0008), nuclear grade 3 (p=0.0015), a Ki-67 labeling index >10% (p=0.02) and tumor size (p=0.048), and in a direct fashion with estrogen (p=0.0003) and progesterone receptor expression (p=0.0002). mRNA expression of the Bcl-2 gene showed a significant inverse correlation with c-erb-B2 (p=0.016) and p53 (p=0.014) expression, as well as with a nuclear grade 3 (p=0.006), and a direct correlation with estrogen (p=0.0004) and progesterone (p=0.001) receptor expression, as well as with nodal invasion (p=0.04). Conclusion: The study of Bcl-2 expression in breast cancer by means of either immunohistochemistry or RT-PCR yields very similar results. In spite of its role opposing tumor cell death, Bcl-2 is associated with biological features of the tumors which define a better intrinsic prognosis, such as hormone receptor expression, low proliferation and absence of c-erb-B2 and mutant p53 expression. This may in great part explain why Bcl-2 expression has been invariably found to correlate with a better prognosis of breast cancer.