B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome.
B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.
Howard Hughes Medical Institute, Immunology Program and Ludwig Center for Cancer Immunotherapy, and Departments of Surgery and Urology, Pathology, and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Xingxing
X
Zang
R Houston
RH
Thompson
Hikmat A
HA
Al-Ahmadie
Angel M
AM
Serio
Victor E
VE
Reuter
James A
JA
Eastham
Peter T
PT
Scardino
Padmanee
P
Sharma
James P
JP
Allison
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000032:analysis / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D016019:Survival Analysis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; D011971:Receptors, Immunologic; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human