Prognostic role of Ape/Ref-1 subcellular expression in stage I-III breast carcinomas

The purpose of the study was to evaluate the prognostic role of the DNA repair protein APE/Ref-1 in breast carcinomas. Immunohistochemical analysis for APE/Ref-1 was performed in a series of 133 consecutive stage I-III breast carcinomas. The relationship between APE/Ref-1 and other prognostic and predictive factors such as tumor size, nodal status, histologic grade, p53 expression, hormonal receptor status, vascular invasion and necrosis was investigated. The prognostic value of APE/Ref-1 was studied by univariate and multivariate analysis. The predominant pattern of APE/Ref-1 immunohistochemical expression was nuclear, although cytoplasmic and mixed nuclear/cytoplasmic localization was also observed. The percentage of cells with APE/Ref-1 cytoplasmic stain directly correlated with the percentage of p53 positive cases (rho=0.28, p=0.013). The small group of women whose tumors showed mixed nuclear/cytoplasmic APE/Ref-1 localization (n=5) experienced a significantly poorer survival (p=0.014) and Cox proportional hazard model analysis identified APE/Ref-1 as an independent prognostic factor. The results suggest that subcellular localisation of APE/Ref-1 may influence the aggressiveness of breast carcinomas.