Bcl-2 oncoprotein expression in breast cancer, its relation to estrogen and progesterone receptors and other prognostic factors

Abstract

Aims of the study:To evaluate the expression of the Bcl-2 oncoprotein in patients with primary breast cancer, to correlate it with estrogen and progesterone receptors and various prognostic parameters. Patients and methods: Fifty two cases of primary breast cancer in which the estrogen and progesterone receptors statuses were previously tested by immuno-histochemical staining, were included in this retrospective study. The cases were collected from Al-Jamhori Teaching Hospital, Nineveh Private Hospital and Private laboratories. The expression of Bcl-2 oncoprotein was evaluated immunohistochemically; the findings were correlated with the estrogen and progesterone receptors, the age of the patients, size, type and grade of the tumor, lymph node status and vascular invasion. Results: Bcl-2 oncoprotein was detected in 24 cases of primary breast cancer (46.2%). In this study the majority of estrogen and progesterone receptors positive cases, (87.5%) and (83.3%) respectively, showed positive Bcl-2 oncoprotein expression, (P<0.001) and (P=0.0002) respectively. A significant association was found between Bcl-2 and tumor type (P=0.017). Bcl-2 oncoprotein was directly correlated with the age of the patients (P=0.0047), and inversely with the grade of the tumor and vascular invasion (P value = 0.0092, <0.001) respectively. No significant correlation with tumor size nor with lymph node status could be found, (P=0.078) and (P=0.19) respectively. Conclusions: Bcl-2 oncoprotein was positive in 46.2% of primary breast cancer. This study revealed a significantly direct correlation between the Bcl-2 and the estrogen and progesterone receptors. A significant association was found between Bcl-2 oncoprotein and tumor type. Bcl-2 was directly related to the age of the patients, and inversely related to the grade of the tumor and vascular invasion.

Immunoexpression of Bcl-2 in Breast Carcinoma: Association with Clinicopathological Parameters

“…(33) In this study 67.6% of estrogen receptor positive cases showed Bcl-2 positivity and 74.5% of progesterone receptor positive cases showed Bcl-2 positivity, a significant relation was found between estrogen and progesterone receptors and Bcl-2 expression, this is in agreement with other studies. (3,7,9,17,24,26,27,33,34) This observation confirms the hypothesis that this protein, like PR, is under oestrogen regulation via ER. Binding of estrogen to ER causes its phosphorylation and dimerization followed by transcription of a variety of genes, including secreted growth and angiogenic factors, as well as PR and Bcl-2.…”

“…Estrogen receptors were positive in 71% cases of breast carcinoma in which 67.6% of cases showed strong Bcl-2 positive staining as shown in figure (6), statistically there was significant relation between estrogen receptor positivity and Bcl-2 immunoreactivity (P value = 0.030). Progesterone receptors were positive in 59% cases of breast carcinoma in which 74.5% of cases showed strong positive staining for Bcl-2 as shown in Figure (7)…”

“…The materials for the procedure were obtained from Dakocytomation (Monoclonal Mouse Anti-Human bcl-2 Oncoprotein) Clone: 124 Isotype: IgG1, kappa (code N1587), and the Detection system EnVision G|2 System/AP, Rabbit/ Mouse (code K5007). Scoring of Bcl-2: Positive expression of Bcl-2 gives cytoplasmic staining, positive cells were determined by examining 10 HPF with (400x), the extent of Bcl-2 immunostaining was assessed as follows: 7 Intensity score: (0= none, 1= weak, 2= intermediate, 3= strong). Proportion Score: (0=0%, 1= <10%, 2= 10-50%, 3=51-80%, 4= >80%).…”

“…It has been localized in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes of hematopoietic and lymphoid cells, neurons, many epithelial cells, and endocrine influenced glandular epithelium such as the thyroid, prostate, endometrium, and breast. 7 Bcl-2 was first identified as an antiapoptotic proto-oncogene in non-Hodgkin's lymphoma cells 8 , and it was involved in the t(14;18) chromosomal translocation found in many follicular Bcell lymphoma. 9 Bcl-2 is localized to the luminal cells of the normal breast, which are considered to be the origin of malignant breast disease.…”