Evaluation of Immunohistochemical Anti-apoptotic Bcl-2 and Pro-apoptotic Bax Gene Products in Breast Carcinoma (original) (raw)
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Association of Bcl2 Immunohistochemical Expression with Breast Tumors Types
This is a descriptive case study aimed to study the role of Bcl2 expression in differentiation between malignant and benign breast tumors. Forty paraffin embedded blocks previously diagnosed as breast tumors were collected. Samples include 30(75%) malignant tumors, including invasive ductal carcinoma 27(67.5%) samples, micro papillary carcinoma 1(2.5%) sample, metaplastic squamous cell carcinoma 1(2.5%) sample, and low grade sarcoma 1 (2.5%) sample. And 10(25%) samples were benign tumors, including fibroadenoma 7(17.5%) samples, gynaecomastia 1(2.5%) sample, ductal ectasia 1(2.5%) sample, and granulomatous mastitis 1(2.5%) sample. One section of 3μm thickness was cut from each paraffin block by rotary microtome and stained by immunohistochemical method (modified new indirect method) for detection of Bcl2. Data collected from patients files and results were analyzed using SPSS computer program. The patient's age ranged between 16 and 70 years with mean age of 43 years, most patients were less than 40 years representing 24(60%) and the remaining 16 (40%) patients were more than 40 years. Immunohistochemical expression of Bcl2 was revealed positive result in 14/30 samples and negative result in 16/30 samples in malignant, while all benign tumors gave negative result for Bcl2, with significant statistical association between Bcl2 expression and histopathology diagnosis (P=0.007). 13 breast cancers Bcl2 positive samples, 3(11.1%) samples were grade 1, 3(11.1%) samples were grade11 and 7(25.9%) samples grade111, and negative in 10(37%) samples. With statistical association between Bcl2 expression and grade of cancer (P=0.035). This study concludes that there is association between Bcl2 expression and malignant tumors of breast. There is association between Bcl2 expression and the grade of cancer.
Bax immunohistochemical expression in breast carcinoma: A study with long term follow-up
International Journal of Cancer, 1998
Bax and Bc12 are functionally antagonistic proteins which control apoptosis, whose expression in human tumours could be of prognostic value. We evaluated Bax and Bcl2 expression in 239 breast carcinomas (99 N0, 140 N1/2) with long term follow-up (median 79 months, range 11-140) in relation to clinico-pathologic parameters, clinical outcome, adjuvant therapy and expression of oestrogen receptor protein and p53. The prognostic value of Bax was investigated in the whole series of patients and in subgroups of homogeneously staged and treated patients (i.e., node-negative, N1/2 CMFtreated, N1/2 tamoxifen-treated). Bax immunostaining was cytoplasmic and heterogeneous. Cases were scored as Baxpositive if there were more than 20% reacting cells. High Bax expression was associated with positive nodal status (p ؍ 0.03) and high Bcl2 expression (p ؍ 0.01) and was more frequent in high-grade tumours. In the node-negative subgroup, Bax expression was associated with small tumour size. No association was seen with other parameters or with clinical outcome in any subgroup of patients. Since the apoptotic rate of a tumour is influenced by the ratio Bcl2/Bax, we investigated the combined effects of Bax and Bcl2 expression in relation to clinical outcome. However, no differences in survival were seen in the Bcl2-negative and Bcl2-positive groups when they were subdivided on the basis of the level of Bax expression and vice versa. In experimental systems, p53 is a direct transcriptional activator of the human bax gene. However, we could not observe any relation between Bax and p53 expression. We investigated whether the combined p53/Bax expression could have any prognostic value since it is predicted that tumours with normal p53 expression and concurrent high levels of Bax should be less aggressive and more susceptible to therapy. However, while p53 itself was of prognostic value, Bax expression was not related to prognosis in p53-negative or in p53-positive groups. Int. J. Cancer (Pred. FIGURE 3 -Bc12 immunoreactivity in infiltrating duct carcinoma of the breast. Scale bar, 70 µm.
Annals of the New York Academy of Sciences, 2008
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.
Expression of bcl-2-like immunoreactivity in the normal breast and in breast cancer
The Breast, 1993
The expression of bcl-2 protein was analyzed in 336 breast tissue specimens (313 malignant and 23 normal) by immunohistologic staining of frozen and paraffin-fixed tissue. All normal breast specimens and up to 89% of breast carcinoma cases, depending upon the method of tissue fixation, showed positive staining. There was no difference in staining between different tumour types or grades. There was striking heterogeneity of bcl-Zlike staining in a large number of specimens of both normal and malignant tissues. In most cases, bcl-Zlike protein staining was weaker in normal breast epithelium than in adjacent neoplastic cells suggesting that some tumours overexpress the protein. In normal breast epithelium, myoepithelial cells were negative in the majority of cases. A consistent finding was the absence of any positivity in apocrine metaplasia. The pattern of bcl-Zlike staining was not affected by the phase of the menstrual cycle in normal breast biopsies. The bcl-2 protein is known to inhibit programmed cell death and may be important in the expansion of a tumour cell population by contributing to the malignant phenotype of breast cancer.
Journal of Pharmaceutical Research International, 2021
Background: The incidence of Breast cancers has overtaken the cervical cancers amongst Indian females. Invasive Ductal carcinoma is reported to be the most common form of breast cancer. Bcl-2 has been studied extensively as a common factor in the pathogenesis of solid tumours including breast cancer. Bcl-2 is an anti-apoptotic protein normally expressed in mammary tissue and is up-regulated by oestrogen in breast cancer through direct consequence of transcriptional induction. The present study attempts to look into Bcl-2 immunoexpression as a key parameter for predicting the treatment outcomes and recurrence of Invasive Ductal Carcinoma. Methodology : This will be an observational study conducted in Department of Pathology, JNMC, Wardha. The study will include clinicopathological detailing of 50 mastectomy specimens of Invasive ductal carcinoma, detailed sectioning of tumour tissues, histopathological BR-grading and molecular subtyping using Bcl-2 immunohistochemistry. Expected ...
Neoplasma, 2012
The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma. 83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome.
Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer
Breast Cancer Research and Treatment, 2006
Alterations in the mechanisms of apoptosis are responsible not only for the progression of breast cancer, but for different responses to treatment as well. Among the genes regulators of apoptosis, the tumor suppressor gene p53 and the bcl-2 gene have raised interest for their possible role as predictors of response to therapy and markers of prognosis. The purpose of our study was to prospectively analyze the prognostic value of the expression of p53 and bcl-2 genes in a series of 235 consecutive patients operated on for breast cancer at the Department of General Surgery and Surgical Oncology of the University of Siena, Italy. p53 and bcl-2 expression were evaluated by immunohistochemistry, their association with conventional clinicopathological factors was analyzed by univariate analysis and their prognostic impact was evaluated by multivariate analysis. p53 and bcl-2 were detected respectively in 15.7 and 75.7% of cases, and resulted significantly related to presence of estrogen receptors for p53 over-expression and presence of peritumor lymphovascular invasion (LVI) for bcl-2 expression. With a median follow-up of 79 months, an independent negative prognostic impact on disease free and overall survival was observed for presence of LVI, absence of bcl-2 expression and number of involved axillary lymphnodes. The expression of bcl-2 improved the prognosis of LVI positive tumors up to values similar to LVI negative cases, while its absence associated to presence of LVI resulted in a poor outcome with only 28% of patients alive at 8 years. These data may indicate that expression of bcl-2 is a marker of breast cancers with reduced capability of distant colonization, even in presence of LVI, and may be particularly useful in the clinical setting, allowing to identify a subset of patients with an high risk of relapse.
Pathology & Oncology Research, 2000
This study describes the incidence of Bax protein expression in a series of 106 cases of breast cancer including 56 cases of ductal carcinoma in situ (DCIS) and 50 cases of invasive ductal carcinoma (IDC). Relationships of Bax expression to the histological grades of DCIS & IDC, and to the expression of Ki67, ER, p53, cerbB2 & Bcl2 are described. The expression of Bax, Ki67, ER, p53, cerbB2 and Bcl2 proteins is determined immunohistochemically. Cases were regarded positive for Bax, Bcl2 and cerbB2 when they showed either moderate or strong staining for these markers. The nuclear stains (Ki67, ER, and p53) were quantified in terms of percentage positive cells and cases for ER and p53 were considered positive when more than 10% cells were labelled. DCIS were graded histologically as well (n=18), intermediately (n=18), and poorly differentiated (n=20) Invasive ductal carcinoma was graded as grade I (well-differentiated) n=7, grade II (intermediate) n=24 and grade III (poorly differentiated) n=19. 65/106 cases (61%) were Bax positive including 37/56 (66%) of DCIS and 28/50 (56%) of IDC. Bax expression did not correlate to increasing histological grades of either DCIS or IDC. It did not correlate to Ki67, ER, p53 or cerbB2 but positive correlation was seen with Bcl2 (p= 0.003). Bcl2 immunostaining displayed a negative correlation with increasing histological grades both of DCIS and IDC (p=0.026), (p=0.041) respectively. There was a trend of negative correlation of Bcl2 with Ki67 (p=0.062). It correlated positively with Bax (p=0.003) and ER (p<0.0001). Results suggest that the regulation of apoptosis is important in ductal carcinoma in situ of the breast as well as invasive ductal carcinomas. Bcl2 is associated with good prognostic markers in both DCIS and IDC, whereas the regulation of Bax is complex and does not necessarily correlate with mutant p53.