Association of Androgen Receptor Expression on Tumor Cells and PD-L1 Expression in Muscle-Invasive and Metastatic Urothelial Carcinoma: Insights for Clinical Research

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Abstract

BACKGROUND: Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients.

PATIENTS AND METHODS: From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1% cutoff of TC). PD-L1 coexpression, by TC or immune cells (1% cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted.

RESULTS: A total of 110 patients had tumor samples stained. Overall, 48 (43.6%) had AR-expressing TC: 19 (17.3%) had 1%-5% expression, 15 (13.6%) 5%-25% expression, and 14 (12.7%) > 25% expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable (P = .477) and multivariable (P = .505) analyses.

CONCLUSION: AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti-PD-L1 therapy.

Original languageEnglish
Pages (from-to)e403-e410
JournalClinical Genitourinary Cancer
Volume16
Issue number2
DOIs
Publication statusPublished - Apr 2018

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Androgen Receptors
Cell Death
Ligands
Carcinoma
Muscles
Research
Neoplasms
Platinum
Survival
Immunohistochemistry
Fluorescence In Situ Hybridization
Proportional Hazards Models
Genes
Exons
Chromosomes
Neoplasm Metastasis
Drug Therapy
Mutation

Cite this

@article{6fb20cd488124be0bbace82ae7411fc7,
title = "Association of Androgen Receptor Expression on Tumor Cells and PD-L1 Expression in Muscle-Invasive and Metastatic Urothelial Carcinoma: Insights for Clinical Research",
abstract = "BACKGROUND: Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients.PATIENTS AND METHODS: From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1{\%} cutoff of TC). PD-L1 coexpression, by TC or immune cells (1{\%} cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted.RESULTS: A total of 110 patients had tumor samples stained. Overall, 48 (43.6{\%}) had AR-expressing TC: 19 (17.3{\%}) had 1{\%}-5{\%} expression, 15 (13.6{\%}) 5{\%}-25{\%} expression, and 14 (12.7{\%}) > 25{\%} expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable (P = .477) and multivariable (P = .505) analyses.CONCLUSION: AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti-PD-L1 therapy.",
author = "Andrea Necchi and {Lo Vullo}, Salvatore and Patrizia Giannatempo and Daniele Raggi and Federica Perrone and Nicola Nicolai and Mario Catanzaro and Davide Biasoni and Tullio Torelli and Luigi Piva and Silvia Stagni and Roberto Salvioni and Luigi Mariani and Maurizio Colecchia",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2018",
month = "4",
doi = "10.1016/j.clgc.2017.09.016",
language = "English",
volume = "16",
pages = "e403--e410",
journal = "Clinical Genitourinary Cancer",
issn = "1558-7673",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Association of Androgen Receptor Expression on Tumor Cells and PD-L1 Expression in Muscle-Invasive and Metastatic Urothelial Carcinoma

T2 - Insights for Clinical Research

AU - Necchi, Andrea

AU - Lo Vullo, Salvatore

AU - Giannatempo, Patrizia

AU - Raggi, Daniele

AU - Perrone, Federica

AU - Nicolai, Nicola

AU - Catanzaro, Mario

AU - Biasoni, Davide

AU - Torelli, Tullio

AU - Piva, Luigi

AU - Stagni, Silvia

AU - Salvioni, Roberto

AU - Mariani, Luigi

AU - Colecchia, Maurizio

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2018/4

Y1 - 2018/4

N2 - BACKGROUND: Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients.PATIENTS AND METHODS: From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1% cutoff of TC). PD-L1 coexpression, by TC or immune cells (1% cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted.RESULTS: A total of 110 patients had tumor samples stained. Overall, 48 (43.6%) had AR-expressing TC: 19 (17.3%) had 1%-5% expression, 15 (13.6%) 5%-25% expression, and 14 (12.7%) > 25% expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable (P = .477) and multivariable (P = .505) analyses.CONCLUSION: AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti-PD-L1 therapy.

AB - BACKGROUND: Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients.PATIENTS AND METHODS: From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1% cutoff of TC). PD-L1 coexpression, by TC or immune cells (1% cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted.RESULTS: A total of 110 patients had tumor samples stained. Overall, 48 (43.6%) had AR-expressing TC: 19 (17.3%) had 1%-5% expression, 15 (13.6%) 5%-25% expression, and 14 (12.7%) > 25% expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable (P = .477) and multivariable (P = .505) analyses.CONCLUSION: AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti-PD-L1 therapy.

U2 - 10.1016/j.clgc.2017.09.016

DO - 10.1016/j.clgc.2017.09.016

M3 - Article

C2 - 29111177

VL - 16

SP - e403-e410

JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

SN - 1558-7673

IS - 2

ER -