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Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer

INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients tre...

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Autores principales: Mahmoud, Ahmed M., Frank, Igor, Orme, Jacob J., Lavoie, Roxane R., Thapa, Prabin, Costello, Brian A., Cheville, John C., Gupta, Sounak, Dong, Haidong, Lucien, Fabrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233321/
https://www.ncbi.nlm.nih.gov/pubmed/35751046
http://dx.doi.org/10.1186/s12894-022-01044-1
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author Mahmoud, Ahmed M.
Frank, Igor
Orme, Jacob J.
Lavoie, Roxane R.
Thapa, Prabin
Costello, Brian A.
Cheville, John C.
Gupta, Sounak
Dong, Haidong
Lucien, Fabrice
author_facet Mahmoud, Ahmed M.
Frank, Igor
Orme, Jacob J.
Lavoie, Roxane R.
Thapa, Prabin
Costello, Brian A.
Cheville, John C.
Gupta, Sounak
Dong, Haidong
Lucien, Fabrice
author_sort Mahmoud, Ahmed M.
collection PubMed
description INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. RESULTS: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1(+)B7-H3(+)). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). CONCLUSIONS: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-022-01044-1.
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spelling pubmed-92333212022-06-26 Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer Mahmoud, Ahmed M. Frank, Igor Orme, Jacob J. Lavoie, Roxane R. Thapa, Prabin Costello, Brian A. Cheville, John C. Gupta, Sounak Dong, Haidong Lucien, Fabrice BMC Urol Research INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. RESULTS: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1(+)B7-H3(+)). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). CONCLUSIONS: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-022-01044-1. BioMed Central 2022-06-24 /pmc/articles/PMC9233321/ /pubmed/35751046 http://dx.doi.org/10.1186/s12894-022-01044-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mahmoud, Ahmed M.
Frank, Igor
Orme, Jacob J.
Lavoie, Roxane R.
Thapa, Prabin
Costello, Brian A.
Cheville, John C.
Gupta, Sounak
Dong, Haidong
Lucien, Fabrice
Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title_full Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title_fullStr Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title_full_unstemmed Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title_short Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
title_sort evaluation of pd-l1 and b7-h3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233321/
https://www.ncbi.nlm.nih.gov/pubmed/35751046
http://dx.doi.org/10.1186/s12894-022-01044-1
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