Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients

INTRODUCTION: Deregulation of Polycomb member Bmi-1 is involved in cell proliferation and human oncogenesis. Modulation of Bmi-1 is found in several tumor tissues, including primary breast carcinomas; however, analysis of Bmi-1 in plasma of cancer patients has not been reported. This is the first study that evaluates Bmi-1 in plasma by using a large series of primary breast carcinomas to investigate the presence at diagnosis of detectable Bmi-1 mRNA in plasma and possible correlations between this event and a series of clinical-pathological parameters of the tumors. METHODS: Bmi-1 expression levels were quantified in plasma of 111 breast cancer patients and in 20 healthy controls by real-time quantitative polymerase chain reaction. RESULTS: Cancer patients with the presence of Bmi-1 mRNA in plasma had higher levels of Bmi-1 expression than healthy controls with Bmi-1 mRNA in plasma. The higher expression levels of Bmi-1 correlated with well-established markers of poor clinical outcome in breast cancer such as positive p53 immunostaining and negative progesterone receptors. Moreover, we described for the first time a statistically significant correlation between Bmi-1 expression in plasma of breast cancer patients and disease-free and overall survival in advanced stages. CONCLUSION: Our results suggest that levels of Bmi-1 expression may be a surrogate marker of poor prognosis and may become clinically useful as noninvasive diagnostic markers.