Down‐regulation of Bax‐interacting factor‐1 in colorectal adenocarcinoma

Abstract

BACKGROUND. Bax‐interacting factor‐1 (Bif‐1 ) protein is a member of the endophilin B family that plays a critical role in apoptosis, autophagy, and mitochondrial morphology. Loss of Bif‐1 suppresses programmed cell death and promotes tumorigenesis. The connection of Bif‐1 to colorectal cancer remains to be evaluated. METHODS. To determine Bif‐1 expression in human colorectal adenocarcinoma (CRC), the authors performed immunohistochemistry using stage‐oriented cancer tissue microarrays containing 102 CRC samples of different stages and 38 samples of normal colorectal mucosa (NR). Formalin‐fixed, paraffin‐embedded core sections on the tissue array were immunostained using the avidin‐biotin‐peroxidase method and the anti‐Bif‐1 murine monoclonal antibody. Bif‐1 staining was scored by 2 independent observers. To examine Bif‐1 mRNA levels, the authors performed DNA microarray analysis of 205 CRC and 10 NR samples. RESULTS. Bif‐1 expression was negative in 22.5% (23 of 102) of CRCs. Moderate to strong Bif‐1 staining was identified in 36.3% (37 of 102) of the tumors, and weak staining was noted in 41.2% (42 of 102). Twenty‐six of 38 (68.4%) NR samples exhibited moderate to strong Bif‐1 immunoreactivity, and none of them was negative. In 12 (31.6%) cases NR demonstrated weak Bif‐1 stain. The mean (median) scores for CRCs and NR differed significantly: 3.2 (3.0) and 5.2 (6.0), respectively (P = .0003). The percentage of cases with negative expression also differed significantly between NR and CRC (P = .002). Decreased Bif‐1 expression in CRCs was confirmed at the mRNA level by microarray analysis. CONCLUSIONS. The authors report the down‐regulation of Bif‐1 during the transition from NR to CRC, a novel finding in agreement with the tumor suppressor function of Bif‐1. Cancer 2008. © 2008 American Cancer Society.