JD Choate, KA Robstad, CE Sheehan, JS Ross and DM Jones
Department of Pathology, Albany Medical College, Albany, NY
Background: Bmi-1 protein expression plays a vital role in cell cycle regulation and senescence, and has been implicated in lymphangiogenesis and carcinogenesis. Bmi-1 oncogene overexpression has been previously identified in several human malignancies including hematologic malignancies, as well as carcinomas including CRC; however, clinicopathologic and prognostic significance of Bmi-1 expression has not been fully elucidated.
Design: Formalin-fixed, paraffin-embedded sections from 153 colorectal adenocarcinomas (CRCs) were immunostained by an automated method (Ventana Medical Systems; Tucson, AZ) using mouse monoclonal Bmi-1 (clone F6; Millipore, Burlington, MA). Nuclear and cytoplasmic immunoreactivity were semi quantitatively evaluated based on both intensity (weak, moderate and intense) and distribution (focal <10%, regional 10 to 50% and diffuse >50%) and results were correlated with clinic-pathologic variables.
Result: Bmi-1 nuclear immunoreactivity was over-expressed in 100/153 (65%) of CRC, while cytoplasmic over-expression was observed in 62/153 (41%). Nuclear overexpression correlated with low tumor grade (77% grade 1 vs 72% grade 2 vs 49% grade 3, p=0.016) and lengthened overall survival (80% alive vs 59% expired, p=0.008). There were no other significant correlations. On multivariate analysis, only pathologic stage at diagnosis independently predicted patient survival.
Conclusion: Bmi-1 overexpression is associated with lower grade CRC’s and significantly correlates with increased overall survival. These findings indicate that Bmi-1 over-expression may be a significant prognostic biomarker that could play a role in the planning of therapy in CRC. Further study of Bmi-1 expression in CRC appears warranted.