Bcl-2 expression and triple negative profile in breast carcinoma

Abstract

Many biomarkers for breast cancer prognosis have been proposed during the last two decades, among which HER2 and oestrogen receptors are of common use in routine clinical practice. However, in recent years, BCL2 has been recognized as an important prognostic parameter in human breast cancer, although its clinical utility is well established. The aim of this study was to examine the protein expression patterns of BCL2, HER2, oestrogen (ER) and progesterone receptors (PR) and to evaluate their correlation with survival and other prognostic parameters such as tumour size, histological grade and metastasis. We used a retrospective study including 84 Tunisian women with breast cancer. Immunohistochemistry was used to measure protein expression levels of several biomarkers. Association with conventional biopathological factors was analysed by SPSS (version13). The expression rates of BCL2, HER2, ER and PR were, respectively, 69, 62, 58.3 and 51.2%. In univariate analyses, BCL2 was highly correlated with both PR (P < 0.001) and ER (P = 0.006) and also with HER2 expression (P = 0.001). The triple negative profile showed a significant association with SBR (P = 0.016) and BCL2 expression (P = 0.02). In multivariate analyses, a significant association was maintained between BCL2 and both PR and ER (P = 0.02 and P = 0.004, respectively). Survival analysis showed that BCL2 expression was positively correlated with patients survival (P = 0.032). A Bayesian network analysis of all the variables confirmed the high value of BCL2 expression as a predictor of survival. As conclusion, BCL2 expression seems to be a very useful factor that should be in combination with HER2 and ER in breast cancer prognosis.

Prognostic significance of Bcl-2 in invasive mammary carcinomas: a comparative clinicopathologic study between “triple-negative” and non–“triple-negative” tumors

“…To our knowledge, this is the first study to document that Bcl-2 positivity has directionally opposite effects on survival in TN and non-TN tumors. Of note, this finding is inconsistent with a previously published report that showed Bcl-2 expression was associated with improved survival in 84 Tunisian patients with TN tumors [5]. These discrepancies may be due to our use of more specific criteria in determination of TN status.…”

“…To our knowledge, the few studies exploring the Bcl-2 expression in TN breast cancer have reported findings consistent with the literature on other molecular tumor types-namely, Bcl-2 positivity is associated with improved survival rates [4,5,20]. Many of these studies, however, were limited by low n values of patients with TN breast cancer.…”

“…It is expressed in 25% to 50% of breast cancers [3] and has been widely reported as a favorable prognostic marker, as its expression has been shown to be associated with improved survival among patients with breast cancer [2,[4][5][6][7] A 2008 meta-analysis found a strongly positive effect of Bcl-2 positivity on disease-free survival and overall survival [2]. Moreover, Bcl-2 expression has been cited as a favorable prognostic marker across multiple breast cancer molecular subtypes [4].…”

Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

“…This is not surprising because a recent study proved that Bcl-2 is a prognostic factor in women with both ER positive and ER negative disease and also in women with both Her2 negative and Her2 positive disease and its positivity is maintained across various molecular subtypes of breast cancer (Dawson et al, 2010). Although the frequency of Bcl-2 expression ranged from 69-73% in previous studies (Dawson et al, 2010;Kallel-Bayoudh et al, 2011), a controversy exists because they found that TNBC tend commonly to have lower Bcl-2 expression compared to non-TNBC (Tawfik et al, 2010;de Ruijter et al, 2011), moreover, Bcl-2 oncogene expression was found to be statistically greater in the ER positive breast tumors compared to ER negative tumors (dos Santos et al, 2008). Such discrepancies between the studies are likely to be due to the wide variation between the methodologies and types of cases studied (Cecka et al, 2008).…”

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

“…It was previously reported that GATA-3 functions as a critical regulator of commitment and maturation of cancer cells in the luminal A epithelial lineage, i.e., the expression of GATA-3 regulates luminal differentiation (37). The anti-apoptotic marker Bcl-2 has been proven to be an independent molecular signature, alone or in combination with Ki-67 as a marker pair, in the luminal type of breast cancer (38)(39)(40)(41)(42).…”