Roth Timothy J, Sheinin Yuri, Lohse Christine M, Kuntz Susan M, Frigola Xavier, Inman Brant A, Krambeck Amy E, McKenney Maureen E, Karnes R Jeffrey, Blute Michael L, Cheville John C, Sebo Thomas J, Kwon Eugene D
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Res. 2007 Aug 15;67(16):7893-900. doi: 10.1158/0008-5472.CAN-07-1068. Epub 2007 Aug 8.
B7 coregulatory ligands can be aberrantly expressed in human disease. In the context of cancer, these ligands may act as antigen-specific inhibitors of T-cell-mediated antitumoral immunity. We recently reported that B7-H1 expression by carcinomas of the kidney and bladder portends aggressive disease and diminished survival. The expression of these proteins in prostate cancer, however, has not been investigated. We evaluated B7-H3 and B7-H1 protein expression in the pathologic specimens of 338 men treated for clinically localized prostate cancer between 1995 and 1998 with radical retropubic prostatectomy. Expression levels of B7-H3 in prostate cancer were correlated with pathologic indicators of aggressive cancer as well as clinical outcome. We report that B7-H3 is uniformly and aberrantly expressed by adenocarcinomas of the prostate, high-grade prostatic intraepithelial neoplasia, and four prostate cancer cell lines, whereas B7-H1 is rarely expressed. B7-H3 is expressed by benign prostatic epithelia, although at a more reduced level relative to neoplastic tissue. Increasing levels of B7-H3 intensity correlate with worsening clinicopathologic features of prostate cancer. Marked B7-H3 intensity, present in 67 (19.8%) specimens, confers a >4-fold increased risk of cancer progression after surgery (risk ratio, 4.42; P < 0.001). A survey of normal tissues revealed that B7-H3 is expressed within the liver, urothelium, and fetal kidney. In summary, B7-H3 is aberrantly expressed in all prostate cancers and represents an independent predictor of cancer progression following surgery. Moreover, B7-H3 encompasses a novel diagnostic and potential therapeutic target for the clinical management of prostate cancer and, perhaps, other malignancies as well.
B7共刺激配体在人类疾病中可能会异常表达。在癌症背景下，这些配体可能作为T细胞介导的抗肿瘤免疫的抗原特异性抑制剂。我们最近报道，肾癌和膀胱癌中B7-H1的表达预示着疾病进展迅速且生存期缩短。然而，这些蛋白在前列腺癌中的表达尚未得到研究。我们评估了1995年至1998年间接受根治性耻骨后前列腺切除术治疗的338例临床局限性前列腺癌男性患者病理标本中B7-H3和B7-H1蛋白的表达情况。前列腺癌中B7-H3的表达水平与侵袭性癌症的病理指标以及临床结局相关。我们报告称，B7-H3在前列腺腺癌、高级别前列腺上皮内瘤变以及四种前列腺癌细胞系中均呈一致且异常表达，而B7-H1很少表达。B7-H3在良性前列腺上皮中也有表达，尽管相对于肿瘤组织其表达水平较低。B7-H3强度增加与前列腺癌临床病理特征的恶化相关。67例（19.8%）标本中存在明显的B7-H3强度，这使得术后癌症进展风险增加了4倍以上（风险比为4.42；P<0.001）。对正常组织的一项调查显示，B7-H3在肝脏、尿路上皮和胎儿肾脏中表达。总之，B7-H3在所有前列腺癌中均异常表达，是术后癌症进展的独立预测指标。此外，B7-H3为前列腺癌以及或许其他恶性肿瘤的临床管理提供了一个新的诊断和潜在治疗靶点。
