B7-H3 ligand expression by prostate cancer : A novel marker of prognosis and potential target for therapy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2007-08, Vol.67 (16), p.7893-7900
• Main Authors: ROTH, Timothy J, SHEININ, Yuri, CHEVILLE, John C, SEBO, Thomas J, KWON, Eugene D, LOHSE, Christine M, KUNTZ, Susan M, FRIGOLA, Xavier, INMAN, Brant A, KRAMBECK, Amy E, MCKENNEY, Maureen E, KARNES, R. Jeffrey, BLUTE, Michael L
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Antineoplastic agents; B7 Antigens; Biological and medical sciences; Disease-Free Survival; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prostatectomy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Receptors, Immunologic - biosynthesis; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-07-1068

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.