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GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States

GSTP1 is a member of the Glutathione-S-transferase (GST) family silenced by CpG island DNA hypermethylation in 90–95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenoca...

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Autores principales: Vidal, Igor, Zheng, Qizhi, Hicks, Jessica L., Chen, Jiayu, Platz, Elizabeth A., Trock, Bruce J., Kulac, Ibrahim, Baena-Del Valle, Javier A., Sfanos, Karen S., Ernst, Sarah, Jones, Tracy, Maynard, Janielle P., Glavaris, Stephanie A., Nelson, William G., Yegnasubramanian, Srinivasan, De Marzo, Angelo M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244883/
https://www.ncbi.nlm.nih.gov/pubmed/34191807
http://dx.doi.org/10.1371/journal.pone.0241934
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author Vidal, Igor
Zheng, Qizhi
Hicks, Jessica L.
Chen, Jiayu
Platz, Elizabeth A.
Trock, Bruce J.
Kulac, Ibrahim
Baena-Del Valle, Javier A.
Sfanos, Karen S.
Ernst, Sarah
Jones, Tracy
Maynard, Janielle P.
Glavaris, Stephanie A.
Nelson, William G.
Yegnasubramanian, Srinivasan
De Marzo, Angelo M.
author_facet Vidal, Igor
Zheng, Qizhi
Hicks, Jessica L.
Chen, Jiayu
Platz, Elizabeth A.
Trock, Bruce J.
Kulac, Ibrahim
Baena-Del Valle, Javier A.
Sfanos, Karen S.
Ernst, Sarah
Jones, Tracy
Maynard, Janielle P.
Glavaris, Stephanie A.
Nelson, William G.
Yegnasubramanian, Srinivasan
De Marzo, Angelo M.
author_sort Vidal, Igor
collection PubMed
description GSTP1 is a member of the Glutathione-S-transferase (GST) family silenced by CpG island DNA hypermethylation in 90–95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on tissue microarrays (TMAs) with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). In terms of association with other molecular alterations, GSTP1 positivity was enriched in ERG positive cancers among Black men. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that GSTP1-positive prostate cancers are substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men.
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spelling pubmed-82448832021-07-12 GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States Vidal, Igor Zheng, Qizhi Hicks, Jessica L. Chen, Jiayu Platz, Elizabeth A. Trock, Bruce J. Kulac, Ibrahim Baena-Del Valle, Javier A. Sfanos, Karen S. Ernst, Sarah Jones, Tracy Maynard, Janielle P. Glavaris, Stephanie A. Nelson, William G. Yegnasubramanian, Srinivasan De Marzo, Angelo M. PLoS One Research Article GSTP1 is a member of the Glutathione-S-transferase (GST) family silenced by CpG island DNA hypermethylation in 90–95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on tissue microarrays (TMAs) with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). In terms of association with other molecular alterations, GSTP1 positivity was enriched in ERG positive cancers among Black men. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that GSTP1-positive prostate cancers are substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men. Public Library of Science 2021-06-30 /pmc/articles/PMC8244883/ /pubmed/34191807 http://dx.doi.org/10.1371/journal.pone.0241934 Text en © 2021 Vidal et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vidal, Igor
Zheng, Qizhi
Hicks, Jessica L.
Chen, Jiayu
Platz, Elizabeth A.
Trock, Bruce J.
Kulac, Ibrahim
Baena-Del Valle, Javier A.
Sfanos, Karen S.
Ernst, Sarah
Jones, Tracy
Maynard, Janielle P.
Glavaris, Stephanie A.
Nelson, William G.
Yegnasubramanian, Srinivasan
De Marzo, Angelo M.
GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title_full GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title_fullStr GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title_full_unstemmed GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title_short GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States
title_sort gstp1 positive prostatic adenocarcinomas are more common in black than white men in the united states
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244883/
https://www.ncbi.nlm.nih.gov/pubmed/34191807
http://dx.doi.org/10.1371/journal.pone.0241934
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