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Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas

We have described a rare group of prostate adenocarcinomas that show aberrant expression of p63, a protein strongly expressed in prostatic basal cells and absent from usual-type acinar prostate cancers. The partial basal-like immunophenotype of these tumors is intriguing in light of the persistent d...

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Autores principales: Tan, Hsueh-Li, Haffner, Michael C., Esopi, David M., Vaghasia, Ajay M., Giannico, Giovanna A., Ross, Hillary M., Ghosh, Susmita, Hicks, Jessica, Zheng, Qizhi, Sangoi, Ankur R., Yegnasubramanian, Srinivasan, Osunkoya, Adeboye O., De Marzo, Angelo M., Epstein, Jonathan I., Lotan, Tamara L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344845/
https://www.ncbi.nlm.nih.gov/pubmed/25216229
http://dx.doi.org/10.1038/modpathol.2014.115
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author Tan, Hsueh-Li
Haffner, Michael C.
Esopi, David M.
Vaghasia, Ajay M.
Giannico, Giovanna A.
Ross, Hillary M.
Ghosh, Susmita
Hicks, Jessica
Zheng, Qizhi
Sangoi, Ankur R.
Yegnasubramanian, Srinivasan
Osunkoya, Adeboye O.
De Marzo, Angelo M.
Epstein, Jonathan I.
Lotan, Tamara L.
author_facet Tan, Hsueh-Li
Haffner, Michael C.
Esopi, David M.
Vaghasia, Ajay M.
Giannico, Giovanna A.
Ross, Hillary M.
Ghosh, Susmita
Hicks, Jessica
Zheng, Qizhi
Sangoi, Ankur R.
Yegnasubramanian, Srinivasan
Osunkoya, Adeboye O.
De Marzo, Angelo M.
Epstein, Jonathan I.
Lotan, Tamara L.
author_sort Tan, Hsueh-Li
collection PubMed
description We have described a rare group of prostate adenocarcinomas that show aberrant expression of p63, a protein strongly expressed in prostatic basal cells and absent from usual-type acinar prostate cancers. The partial basal-like immunophenotype of these tumors is intriguing in light of the persistent debate surrounding the cell-of-origin for prostate cancer, however their molecular phenotype is unknown. We collected 37 of these tumors on radical prostatectomy and biopsy and assessed subsets for a diverse panel of molecular markers. The majority of p63-expressing tumors were positive for the ΔNp63 isoform (6/7) by immunofluorescence and p63 mRNA (7/8) by chromogenic in situ hybridization. Despite p63 positivity, these tumors uniformly expressed luminal-type cytokeratin proteins such as CK18 (13/13), CK8 (8/8) and markers of androgen axis signaling commonly seen in luminal cells, including androgen receptor (10/11), NKX3.1 (8/8) and prostein (12/13). Conversely, basal cytokeratins such as CK14 and CK15 were negative in all cases (0/8) and CK5/6 was weakly and focally positive in 36% (4/11) of cases. Pluripotency markers including β-catenin, Oct4 and c-kit were negative in p63-expressing tumors (0/11). Despite nearly universal expression of androgen receptor and downstream androgen signaling targets, p63-expressing tumors lacked ERG rearrangements by fluorescence in situ hybridization (0/14) and ERG protein expression (0/37). No tumors expressed SPINK1 or showed PTEN protein loss (0/19). Surprisingly, 74% (14/19) of p63-expressing tumors expressed GSTP1 protein at least focally, and 33% (2/6) entirely lacked GSTP1 CpG island hypermethylation by bisulfite sequencing. In contrast to usual prostatic adenocarcinomas, prostate tumors with p63-expression show a mixed luminal/basal immunophenotype, uniformly lack ERG gene rearrangement and frequently express GSTP1. These data strongly suggest that p63-expressing prostate tumors represent a molecularly distinct subclass and further study of this rare tumor type may yield important insights into the role of p63 in prostatic biology and the prostate cancer cell-of-origin.
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spelling pubmed-43448452015-09-01 Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas Tan, Hsueh-Li Haffner, Michael C. Esopi, David M. Vaghasia, Ajay M. Giannico, Giovanna A. Ross, Hillary M. Ghosh, Susmita Hicks, Jessica Zheng, Qizhi Sangoi, Ankur R. Yegnasubramanian, Srinivasan Osunkoya, Adeboye O. De Marzo, Angelo M. Epstein, Jonathan I. Lotan, Tamara L. Mod Pathol Article We have described a rare group of prostate adenocarcinomas that show aberrant expression of p63, a protein strongly expressed in prostatic basal cells and absent from usual-type acinar prostate cancers. The partial basal-like immunophenotype of these tumors is intriguing in light of the persistent debate surrounding the cell-of-origin for prostate cancer, however their molecular phenotype is unknown. We collected 37 of these tumors on radical prostatectomy and biopsy and assessed subsets for a diverse panel of molecular markers. The majority of p63-expressing tumors were positive for the ΔNp63 isoform (6/7) by immunofluorescence and p63 mRNA (7/8) by chromogenic in situ hybridization. Despite p63 positivity, these tumors uniformly expressed luminal-type cytokeratin proteins such as CK18 (13/13), CK8 (8/8) and markers of androgen axis signaling commonly seen in luminal cells, including androgen receptor (10/11), NKX3.1 (8/8) and prostein (12/13). Conversely, basal cytokeratins such as CK14 and CK15 were negative in all cases (0/8) and CK5/6 was weakly and focally positive in 36% (4/11) of cases. Pluripotency markers including β-catenin, Oct4 and c-kit were negative in p63-expressing tumors (0/11). Despite nearly universal expression of androgen receptor and downstream androgen signaling targets, p63-expressing tumors lacked ERG rearrangements by fluorescence in situ hybridization (0/14) and ERG protein expression (0/37). No tumors expressed SPINK1 or showed PTEN protein loss (0/19). Surprisingly, 74% (14/19) of p63-expressing tumors expressed GSTP1 protein at least focally, and 33% (2/6) entirely lacked GSTP1 CpG island hypermethylation by bisulfite sequencing. In contrast to usual prostatic adenocarcinomas, prostate tumors with p63-expression show a mixed luminal/basal immunophenotype, uniformly lack ERG gene rearrangement and frequently express GSTP1. These data strongly suggest that p63-expressing prostate tumors represent a molecularly distinct subclass and further study of this rare tumor type may yield important insights into the role of p63 in prostatic biology and the prostate cancer cell-of-origin. 2014-09-12 2015-03 /pmc/articles/PMC4344845/ /pubmed/25216229 http://dx.doi.org/10.1038/modpathol.2014.115 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Tan, Hsueh-Li
Haffner, Michael C.
Esopi, David M.
Vaghasia, Ajay M.
Giannico, Giovanna A.
Ross, Hillary M.
Ghosh, Susmita
Hicks, Jessica
Zheng, Qizhi
Sangoi, Ankur R.
Yegnasubramanian, Srinivasan
Osunkoya, Adeboye O.
De Marzo, Angelo M.
Epstein, Jonathan I.
Lotan, Tamara L.
Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title_full Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title_fullStr Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title_full_unstemmed Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title_short Prostate Adenocarcinomas Aberrantly Expressing p63 Are Molecularly Distinct from Usual-Type Prostatic Adenocarcinomas
title_sort prostate adenocarcinomas aberrantly expressing p63 are molecularly distinct from usual-type prostatic adenocarcinomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344845/
https://www.ncbi.nlm.nih.gov/pubmed/25216229
http://dx.doi.org/10.1038/modpathol.2014.115
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