Association of immunohistochemical expression of Bcl-2 with estrogen ER-PR receptors and HER2 and Ki67 in breast cancer

Background: Breast carcinoma is among the three most common types of cancer worldwide, including lung cancer and colon cancer, regardless of gender. The Bcl-2 oncogene is involved in a number of malignant neoplasms, includ¬ing leukaemia and lymphoma, through the regulation of the cell apoptosis process. Aim: The main purpose of the present study is to investigate the association of Bcl-2 with other molecular parameters of significant prognostic and predictive value for disease and more specifically the ER and PR receptors, along with HER-2 and Ki-67 (MIB-1). Methodology: Immunohistochemical assessment of Bcl-2, ER and PR receptors, HER-2 and Ki-67 was conducted in a case series of 100 surgically resected primary breast carcinomas and the association of Bcl-2 with the other bi¬omarkers was statistically investigated. Results: High (3+) Bcl-2 expression was observed in 65% of cases, moderate (2+) in 12%, low (1+) in 4% and negative expression in 19%. Association of Bcl-2 with ER-PR receptors and HER2 and Ki67 was conducted with Fisher’s exact and Chi square (x2) test of Cramer's V statistics tests were performed where appropriate. Bcl-2 oncogene was positively and highly associated with estrogen ER receptors (Phi=0.760, p=<0.0001); the findings of the association of Bcl-2 oncogene with PR progesterone receptors were similar: a positive association was found between the two specific biomarkers (Phi=0.626, p=<0.0001). Finally, negative association of Bcl-2 with HER2 (Phi=-0.350, p=<0.0001). Conclusion: Considering the association of Bcl-2 expression with the ex¬pression of genes that are related to therapy prediction (ER and PR) it remains to be ascertained whether Bcl-2 could be used as a potential predictive marker. Moreover, the negative association of Bcl-2 with Ki67 and HER2 should be furthermore investigated for its association with disease outcome and response to targeted therapy. Overall, this study suggests that Bcl-2 should be further tested for its incorporation into a multivariate prediction model for breast cancer therapy. In addition, more investigations are required into targeted anti-Bcl-2 therapy may be used to modify re¬sponses to current breast cancer therapy, in order to reduce resistance.