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Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands....

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Autores principales: Kang, Minyong, Lee, Hyunwoo, Byeon, Sun-Ju, Kwon, Ghee Young, Jeon, Seong Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658449/
https://www.ncbi.nlm.nih.gov/pubmed/34884926
http://dx.doi.org/10.3390/ijms222313125
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author Kang, Minyong
Lee, Hyunwoo
Byeon, Sun-Ju
Kwon, Ghee Young
Jeon, Seong Soo
author_facet Kang, Minyong
Lee, Hyunwoo
Byeon, Sun-Ju
Kwon, Ghee Young
Jeon, Seong Soo
author_sort Kang, Minyong
collection PubMed
description Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.
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spelling pubmed-86584492021-12-10 Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate Kang, Minyong Lee, Hyunwoo Byeon, Sun-Ju Kwon, Ghee Young Jeon, Seong Soo Int J Mol Sci Review Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor. MDPI 2021-12-04 /pmc/articles/PMC8658449/ /pubmed/34884926 http://dx.doi.org/10.3390/ijms222313125 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kang, Minyong
Lee, Hyunwoo
Byeon, Sun-Ju
Kwon, Ghee Young
Jeon, Seong Soo
Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title_full Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title_fullStr Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title_full_unstemmed Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title_short Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate
title_sort genomic features and clinical implications of intraductal carcinoma of the prostate
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658449/
https://www.ncbi.nlm.nih.gov/pubmed/34884926
http://dx.doi.org/10.3390/ijms222313125
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