The p53 positive Bcl‐2 negative phenotype is an independent marker of prognosis in breast cancer

Abstract

The purpose of this work was to determine if the immunohistochemical p53 (1) Bcl-2 (2) phenotype predicts survival in breast cancer patients. Tissue from 819 cases of resected primary breast cancer, presented between 1986 and 1998, were assembled in tissue microarray format. Clinicopathological data and prospective disease specific survival data were collected prospectively and immunohistochemical analyses of p53 and Bcl-2 expression were performed using antibodies DO-7 (p53) and 124 (Bcl-2) employing a standard IHC protocol. The expression data were correlated with clinicopathological variables and outcomes in both univariate (v 2 ) and multivariate (Cox's regression) analyses. Abnormal p53 expression and positive Bcl-2 expression were detected in 29% (193/673) and 46% (307/673) of tumours, respectively. On univariate analysis Bcl-2 expression was correlated with the clinicopathological features of less aggressive disease and loss of Bcl-2 expression correlated with a reduction in survival (log rank 5 11.91; p < 0.001). p53 expression correlated with the clinicopathological features of aggressive cancers and a reduction in survival (log rank 5 17.81; p < 0.001). Nineteen percent (127/673) of tumours displayed a p53 (1) Bcl-2 (2) phenotype. Kaplan-Meier analysis revealed a significant reduction in survival in these cases (log rank 34.01; p < 0.001). Multivariate analysis showed that while neither p53 expression nor Bcl-2 expression alone had independent prognostic significance, the p53 (1) Bcl-2 (2) phenotype remained independently associated with a worse prognosis (HR 1.79 95%CI 1.10-2.89 p 5 0.018).

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

“…However, a missense mutation of p53 results in protein stabilization and accumulation in the nucleus. 65 Expression of p53 has been shown to be associated with poor outcome for patients with IBC in some studies, but has not been shown in others, [66][67][68] particularly when it is in combination with other markers, such as bcl-2 69 or HER2. 70 The different antibodies used in studies seem to produce different results as well.…”

Prognostic Value of p53 and bcl-2 Expression in Patients Treated With Breast Conservative Therapy

“…Aforementioned case-control studies noted a higher risk of distant metastases in patients with p53 expression (9,15). Again, however, consecutive populationbased studies failed to verify the relationship, despite the larger number of patients and events (11,17). In the current study, p53 positivity was an independent prognostic factor predicting distant metastasis-free survival after adjusting conventional clinicopathologic variables including nodal and ER status and treatment-related factors such as the use of chemotherapy and/or hormonal therapy.…”

“…Instead, the combined variable of bcl-2(-)/ER(-) phenotype was proven to be a significant prognostic factor in univariate and multivariate analyses. Given the association between bcl-2 expression and ER status in a number of studies including ours (11,(17)(18)(19), a combined analysis of bcl-2 and ER has already been tried. Callagy et al showed that the risk of death in bcl-2(-)/ER(-) phenotype is higher than those in other three phenotypes (20 Table 2.…”

Reasons for cancer metastasis: A holistic perspective

“…Pathological studies have repeatedly demonstrated that increased apoptosis is associated with a higher grade of malignancy and poor clinical outcome (11)(12)(13)(14)(15). Furthermore, overexpression of the anti-apoptotic protein Bcl-2 is an indicator of a favorable prognosis in breast cancer (16)(17)(18)(19)(20), colorectal cancer (21,22) and non-small-cell lung cancer (NSCLC) (23). Conversely, overexpression of the cell death receptor CD95 is associated with poor clinical outcome in solid tumors, such as renal cell carcinoma and melanoma (24,25).…”