An Immunohistochemistry Study of Tissue Bcl‐2 Expression and Its Serum Levels in Breast Cancer Patients

Abstract

Variations in Bcl-2 expression have been reported in malignant tissues with various origins. In the case of breast cancer, the involvement of Bcl-2 overexpression in tumorigenicity and metastatic potential has been stated. However, association of tumor progression and loss of Bcl-2 in tumor cells is also being investigated. Augmentation of plasma levels of Bcl-2 was speculated in patients with metastatic breast cancer. The present study was designed to evaluate Bcl-2 protein expression in breast tumor paraffin-embedded fixed tissue and sought to investigate association with the Bcl-2 protein release in patient serum, as well as its relationship with clinicopathological features. Immunohistochemistry methods were applied to breast tumor sections from 35 surgically removed patient samples and 35 normal or benign tissue samples. The sera taken from both the patient and control groups were tested for soluble Bcl-2 (BMs244/3 Kit) using ELISA technique. Tumor type, grade, and size and patient menopause status and age were considered to analyze the association between these parameters. The analysis shows that 67.6% of the tumor sections were positive for Bcl-2 expression and 32.4% negative. Bcl-2 protein expression was positive in 57.1% of normal/benign section tumors. The Bcl-2 serum levels were 3.6 +/- 1.1 ng/mL in the patient group and 3.23 +/- 0.06 ng/mL in the control group. A weak correlation was found between Bcl-2 serum levels and tissue expression of the molecules (r= 0.382, P= 0.049). A negative association (but not statically significant) was obtained between Bcl-2 and low-grade stages (r=-0.375, P= 0.08). A positive and significant correlation was shown between Bcl-2 and menopause (r= 0.523, P= 0.005) and between age and serum Bcl-2 (r= 0.488, P= 0.011). Although a majority of the breast tumor tissue expresses Bcl-2, the mean Bcl-2 serum levels were not different between patient and control groups. The present data would lead us to use the Bcl-2 expression in tissue at the level of protein expression or would suggest the use of mRNA levels, but the use of serum levels would be very limited for clinical purposes.

Aspirin-induced Bcl-2 translocation and its phosphorylation in the nucleus trigger apoptosis in breast cancer cells

“…In addition, Bcl-2-positive tumors have been shown to correlate with menopause and ER-positive tumors. 48, 49 The overexpression of Bcl-2 in primary breast carcinomas was associated with improved patient survival, suggesting that Bcl-2 inhibits cancer progression. 50, 51 In agreement with these reports, we found that ER-positive MCF-7 cells expressed a higher level of Bcl-2 and responded well to aspirin (Figures 5a and b).…”

Apoptosis in ischemic heart disease

“…However, no clinical study was performed to examine level of Bcl-2 in serum of AIM patients. In cancer patients, evaluation of Bcl-2 serum levels and its tissue expression showed correlation bordering on statistical significance [57]. …”

Targeted Apoptosis in Breast Cancer Immunotherapy

“…As crucial regulators of mitochondrial apoptotic pathway, several Bcl-2 family members have been found aberrantly expressed or frequently mutated in breast cancers. For example, overexpression of Bcl-2 or Bcl-X L is associated with the development or metastasis of breast carcinomas (Alireza et al, 2008;Martin et al, 2004). In contrast, the absence or inactivation of the pro-apoptotic Bcl-2 family members, such as Bax, Bid and Bim is involved in breast carcinogenesis (Sivaprasad et al, 2007;Sjöström-Mattson et al, 2009;Whelan et al, 2010).…”