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 language | English |
|---|---|
| Pages (from-to) | e403-e410 |
| Journal | Clinical Genitourinary Cancer |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2018 |
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Association of Androgen Receptor Expression on Tumor Cells and PD-L1 Expression in Muscle-Invasive and Metastatic Urothelial Carcinoma : Insights for Clinical Research. / Necchi, Andrea; Lo Vullo, Salvatore; Giannatempo, Patrizia; Raggi, Daniele; Perrone, Federica; Nicolai, Nicola; Catanzaro, Mario; Biasoni, Davide; Torelli, Tullio; Piva, Luigi; Stagni, Silvia; Salvioni, Roberto; Mariani, Luigi; Colecchia, Maurizio.
In: Clinical Genitourinary Cancer, Vol. 16, No. 2, 04.2018, p. e403-e410.Research output: Contribution to journal › Article
}
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 -