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Bax-interacting factor (Bif)-1 protein is a member of the endophilin B family that binds to and activates the proapoptotic Bax protein in response to apoptotic signals. Loss of Bif-1 suppresses the intrinsic pathway of apoptosis and promotes tumorigenesis. We examined the expression levels of Bif-1 protein in human prostate cancer.Thirty-nine archival tissue specimens of human prostate cancer, and a human prostate cancer tissue microarray containing 19 samples of normal prostate, 26 samples of benign prostatic hyperplasias (BPHs), 30 samples of high-grade prostatic intraepithelial neoplasia (PIN), and 153 samples of prostate cancer, were selected for immunohistochemical staining with Bif-1 antibody. The slides were scored by 2 independent observers.Nontissue microarray samples: moderate to strong Bif-1 staining was identified in 38 of 39 prostate cancer samples. In 32 cases, foci of PIN were identified adjacent to prostate cancer samples. Of these, 29 samples (90.6%) showed strong and diffuse Bif-1 staining. Benign prostatic hyperplasias, identified in 27 cases, was weakly Bif-1 positive in 88.9% of cases. Tissue microarray samples: 38.6% (59 of 153) of prostate cancer samples showed moderate to strong Bif-1 expression, and 21.6% (33 of 153) were Bif-1 negative. Bif-1 expression was moderate to strong in 76.7% (23 of 30) of PIN. Bif-1 was weak to moderate in 53.8% (14 of 26) of BPH and negative in 46.2% (12 of 26) of them. Low to moderate Bif-1 was seen in 89.5% of normal prostate samples.The loss of Bif-1 expression in a subset of prostate cancer samples is in agreement with the proapoptotic function of Bif-1. The significance of the increased Bif-1 in a subgroup of prostate cancer samples and in PIN remains to be determined. It seems that Bif-1 has a role in prostate cancer, providing the rationale for using Bif-1 as a target for prostate anticancer therapy.