B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome Journal Article

   

Authors:	Zang, X.; Thompson, R. H.; Al-Ahmadie, H. A.; Serio, A. M.; Reuter, V. E.; Eastham, J. A.; Scardino, P. T.; Sharma, P.; Allison, J. P.
Article Title:	B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome
Abstract:	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. © 2007 by The National Academy of Sciences of the USA.
Keywords:	immunohistochemistry; adult; controlled study; human tissue; protein expression; treatment outcome; aged; survival analysis; unclassified drug; human cell; major clinical study; outcome assessment; follow up; cell protein; prostate cancer; prostatic neoplasms; immune tolerance; prostatectomy; disease progression; antigens, cd; tissue microarray; protein b7 h3; protein b7x; receptors, immunologic; biological tumor markers; antigens, cd80
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	104
Issue:	49
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2007-12-04
Start Page:	19458
End Page:	19463
Language:	English
DOI:	10.1073/pnas.0709802104
PUBMED:	18042703
PROVIDER:	scopus
PMCID:	PMC2148311
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-37649013179&partnerID=40&md5=5bd4e49930be9235f6441b19c562afb8
Notes:	--- - "Cited By (since 1996): 50" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus"

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