Down-regulation of bax-interacting factor 1 in human pancreatic ductal adenocarcinoma

OBJECTIVE: Bax-interacting factor 1 (Bif-1) protein plays a critical role in apoptosis, mitochondrial morphogenesis, and autophagy, and its loss promotes tumorigenesis. The role of Bif-1 in pancreatic cancer has not been studied. METHODS: We determined Bif-1 expression in 82 human pancreatic ductal adenocarcinomas (PDCs) and in 82 nonmalignant pancreatic specimens (NMPs), using immunohistochemistry and tissue microarray. Bif-1 immunostain was semiquantitatively scored on a scale of 0 to 9. RESULTS: Bif-1 scores in NMP were either 6 or 9, with lower scores in only 19 (23.2%) of 82 NMPs. Low Bif-1 expression (score <6) was found in 37 (45.1%) of 82 PDCs, a proportion significantly greater than that found in NMP (P = 0.005). The expression of Bif-1 was twice as likely to be low in PDC as in NMP (relative risk = 1.95, 95% confidence interval, 1.23-3.09). Kaplan-Meier survival estimates showed no difference in survival between patients with low and high Bif-1 expression (P = 0.21, log-rank test). CONCLUSIONS: The expression of Bif-1 is downregulated in a subset of PDC. This novel finding is in agreement with the tumor suppressor function of Bif-1. The lack of association between Bif-1 expression and patient survival may be best explained by the complexity of carcinogenesis.