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

E. Xylinas, B. D. Robinson, L. A. Kluth, B. G. Volkmer, R. Hautmann, R. Küfer, M. Zerbib, Eugene D Kwon, R. H. Thompson, S. A. Boorjian, S. F. Shariat

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalEuropean Journal of Surgical Oncology
Volume40
Issue number1
DOIs
StatePublished - Jan 2014

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Cystectomy
Regulatory T-Lymphocytes
Urinary Bladder
Urothelium
Carcinoma
Neoplasms
Proteins
Mortality
Lymph Node Excision
Multivariate Analysis
Lymph Nodes
Immunohistochemistry
Recurrence

Keywords

  • Bladder cancer
  • Immunohistochemistry
  • Outcomes
  • Prognosis
  • Survival
  • T-cell regulators

ASJC Scopus subject areas

  • Oncology
  • Surgery

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Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. / Xylinas, E.; Robinson, B. D.; Kluth, L. A.; Volkmer, B. G.; Hautmann, R.; Küfer, R.; Zerbib, M.; Kwon, Eugene D; Thompson, R. H.; Boorjian, S. A.; Shariat, S. F.

In: European Journal of Surgical Oncology, Vol. 40, No. 1, 01.2014, p. 121-127.

Research output: Contribution to journalArticle

Xylinas, E, Robinson, BD, Kluth, LA, Volkmer, BG, Hautmann, R, Küfer, R, Zerbib, M, Kwon, ED, Thompson, RH, Boorjian, SA & Shariat, SF 2014, 'Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder', European Journal of Surgical Oncology, vol. 40, no. 1, pp. 121-127. https://doi.org/10.1016/j.ejso.2013.08.023
Xylinas, E. ; Robinson, B. D. ; Kluth, L. A. ; Volkmer, B. G. ; Hautmann, R. ; Küfer, R. ; Zerbib, M. ; Kwon, Eugene D ; Thompson, R. H. ; Boorjian, S. A. ; Shariat, S. F. / Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. In: European Journal of Surgical Oncology. 2014 ; Vol. 40, No. 1. pp. 121-127.
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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.",
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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, Eugene D

AU - Thompson, R. H.

AU - Boorjian, S. A.

AU - Shariat, S. F.

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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.

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KW - Outcomes

KW - Prognosis

KW - Survival

KW - T-cell regulators

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