Reduced Nuclear Expression of Transcription Factor AP-2 Associates with Aggressive Breast Cancer

Purpose: We proposed to investigate the expression and prognostic significance of activator protein 2 (AP-2) in breast cancer. Experimental Design: AP-2 was immunohistochemically analyzed in a prospective, consecutive series of 420 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. AP-2 expression was further compared with clinicopathological parameters and patients’ survival. Results: Nuclear AP-2 expression was lower in carcinomas compared with normal ductal breast epithelium ( P P = 0.048). Cytoplasmic staining was present in 47% of the carcinomas. Low nuclear AP-2 expression level in carcinomas was associated with advanced stage ( P = 0.002), axillary lymph node positivity ( P = 0.012), poor differentiation ( P = 0.001), and recurrences ( P = 0.003). In univariate survival analyses, low nuclear AP-2 expression ( P = 0.0028), advanced stage ( P P P = 0.0498) predicted shorter recurrence-free survival (RFS). Low nuclear AP-2 staining and/or shift to cytoplasmic expression predicted shorter RFS ( P = 0.0050) and breast cancer-related survival (BCRS; P = 0.0314) in univariate analyses. Cytoplasmic expression alone did not have prognostic value. In multivariate analysis, low nuclear AP-2 expression ( P = 0.0292) and advanced stage ( P = 0.0001) were independent predictors of shorter RFS; and stage ( P P = 0.0321) independently predicted BCRS. In the lymph-node positive patients, RFS was independently predicted by stage ( P = 0.0110) and nuclear AP-2 status ( P = 0.0151). Conclusions: AP-2 seems to have a protective role in breast cancer. Low nuclear AP-2 expression was associated with disease progression and increased metastatic capability of the tumor. In addition, reduced nuclear AP-2 expression independently predicted elevated risk of recurrent disease in breast cancer.