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

TY - JOUR

T1 - Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder

AU - Xylinas, E

AU - Robinson, B D

AU - Kluth, L A

AU - Volkmer, B G

AU - Hautmann, R

AU - Küfer, R

AU - Zerbib, M

AU - Kwon, E

AU - Thompson, R H

AU - Boorjian, S A

AU - Shariat, S F

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antigens, CD274

KW - B7 Antigens

KW - Carcinoma, Transitional Cell

KW - Case-Control Studies

KW - Cystectomy

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunohistochemistry

KW - Kaplan-Meier Estimate

KW - Lymph Node Excision

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Programmed Cell Death 1 Receptor

KW - T-Lymphocytes, Regulatory

KW - Tissue Array Analysis

KW - Tumor Markers, Biological

KW - Urinary Bladder Neoplasms

U2 - 10.1016/j.ejso.2013.08.023

DO - 10.1016/j.ejso.2013.08.023

M3 - SCORING: Journal article

C2 - 24140000

VL - 40

SP - 121

EP - 127

JO - EJSO-EUR J SURG ONC

JF - EJSO-EUR J SURG ONC

SN - 0748-7983

IS - 1

ER -