Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder.

Abstract

PURPOSE:

Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings.

MATERIALS AND METHODS:

The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry.

RESULTS:

B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06).

CONCLUSIONS:

B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.

• Authors: E Xylinas, B D Robinson, L A Kluth, B G Volkmer, R Hautmann, R Küfer, M Zerbib, E Kwon, R H Thompson, S A Boorjian, S F Shariat
• Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (Eur J Surg Oncol) Vol. 40 Issue 1 Pg. 121-7 (Jan 2014) ISSN: 1532-2157 [Electronic] England
• PMID: 24140000 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• B7 Antigens
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• CD276 protein, human
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Adult
• Aged
• B7 Antigens (analysis)
• B7-H1 Antigen (analysis)
• Biomarkers, Tumor (analysis)
• Carcinoma, Transitional Cell (chemistry, metabolism, mortality, surgery)
• Case-Control Studies
• Cystectomy (methods)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymph Node Excision
• Male
• Middle Aged
• Predictive Value of Tests
• Programmed Cell Death 1 Receptor (analysis)
• T-Lymphocytes, Regulatory (metabolism)
• Tissue Array Analysis
• Urinary Bladder Neoplasms (chemistry, metabolism, mortality, surgery)