B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy.
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.
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Timothy J
TJ
Roth
Yuri
Y
Sheinin
Christine M
CM
Lohse
Susan M
SM
Kuntz
Xavier
X
Frigola
Brant A
BA
Inman
Amy E
AE
Krambeck
Maureen E
ME
McKenney
R Jeffrey
RJ
Karnes
Michael L
ML
Blute
John C
JC
Cheville
Thomas J
TJ
Sebo
Eugene D
ED
Kwon
D015703:Antigens, CD / Q000096:biosynthesis*; D060887:B7 Antigens; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011971:Receptors, Immunologic / Q000096:biosynthesis*
D015703:Antigens, CD; D060887:B7 Antigens; C423237:CD276 protein, human; D011971:Receptors, Immunologic