Polycomb Transcription Factor Bmi-1 Expression Is Associated with Favorable Outcome in Mammary Carcinoma
JS Ross, E Slodkowska, CE Sheehan. Albany Medical College, Albany, NY
Background: The polycomb transcription factor Bmi-1 originally linked to lymphomagenesis has recently been associated with tumor cell renewal and the stem cell phenotype in experimental breast cancer models. Bmi-1 appears to function as a tumor suppressor by up-regulating the INK4A locus and inducing growth arrest, cellular senescence and apoptosis. The clinical significance of Bmi-1 expression in breast cancer has not been fully examined.
Design: Formalin-fixed, paraffin-embedded tissue sections from 180 cases of invasive mammary carcinoma (130 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC) were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using mouse monoclonal Bmi-1 antibody (Upstate/Millipore, Temecula, CA). Tumor immunoreactivity was semiquantitatively scored based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%) in all cases.
Results: Bmi-1 immunoreactivity was a predominantly nuclear pattern in the majority of cases. Nuclear Bmi-1 positivity correlated with tumor type [36/50 (72%) ILC vs 69/130 (53%) IDC, p= 0.02], low tumor grade [67% grade 1 vs 58% grade 2 vs 36% grade 3, p=0.02], low stage [64% low stage vs 45% advanced stage, p=0.05], ER status [74% ER positive vs 31% ER negative, p<0.0001], PR status [70% PR positive vs 42% PR negative, p<0.0001], and lack of disease recurrence [68% non-recurrent vs 39% recurrent, p<0.0001]. Within the ILC subgroup, nuclear Bmi-1 nuclear immunoreactivity correlated with patient survival [95% alive vs 60% expired, p=0.007]. Within the IDC subgroup, nuclear positivity showed a trend toward correlation with a later age at diagnosis [36% <45 years of age vs 48% diagnosed between 45-55 years of age vs 61% >55 years, p=0.067].
Conclusions: Nuclear Bmi-1 expression in invasive mammary carcinoma is a frequent event and correlates with favorable prognostic factors including advanced patient age, lobular differentiation, low tumor grade, early tumor stage, positive ER and PR status, disease recurrence-free survival (IDC and ILC groups) and overall survival (ILC group only). Further study of Bmi-1 expression in mammary carcinoma appears warranted.
Monday, March 9, 2009 1:00 PM
Poster Session II # 34, Monday Afternoon