Bmi-1 Nuclear Overexpression Correlates with Low Tumor Grade and Lengthened Overall Survival in Colorectal Adenocarcinoma (CRC)

10 11 2009

JD Choate, KA Robstad, CE Sheehan, JS Ross and DM Jones
Department of Pathology, Albany Medical College, Albany, NY

BMI 20x

Bmi-1 Staining at 20x

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.

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