Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer

Abstract

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.

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

“…In this study, Bcl-2 was more frequently associated with negative nodal status (100%) in both TNBC and non-TNBC and there was a significant inverse correlation with nodal positivity in non-TNBC group. This is consistent with the results obtained previously (Park et al, 2002;Neri et al, 2006), which indicate that the expression of Bcl-2 is a marker of breast cancer with reduced capability of distant colonization even in presence of lymphovascular invasion (Neri et al, 2006). On the contrary, Nadler et al (2008), found no association between expression of Bcl-2 and nodal status and Dawson et al (2010), verified the prognostic impact of Bcl-2 positivity regardless of lymph node status.…”

High expression of maspin is associated with early tumor relapse in breast cancer

“…In our breast cancer material, Bcl-2 positivity was significantly lower in the early metastasizing group than in the latest metastasizing group, which is opposite to the results with cytoplasmic maspin and p53. A favorable outcome in Bcl-2-positive breast cancer has been reported in numerous studies [34][35][36]. Also in our study, the expression of Bcl-2 was significantly higher in the primary tumors than in the metastases in the early relapsing group.…”

Expression of Bcl-2 in Breast Cancer: Correlation with Clinicopathological Characteristics and Survival

“…In this regard, our results are in contrast with studies that suggest that bcl-2 expression is a favourable prognostic factor when primary surgical therapy is used. In other studies bcl-2 expression has been found to be an independent predictor of prognosis (7,8,12,10,18,38). However, other studies have shown opposite results (6,25,35,36,47).…”