Human ASH1 expression in prostate cancer with neuroendocrine differentiation

Ida Rapa, Paolo Ceppi, Enrico Bollito, Rosj Rosas, Susanna Cappia, Elisa Bacillo, Francesco Porpiglia, Alfredo Berruti, Mauro Papotti, Marco Volante*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25% of prostate cancers with neuroendocrine differentiation/ untreated, with a significant correlation with the extent of neuroendocrine features (P=0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P=0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivation-treated compared with untreated patients (P=0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two- to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.

OriginalsprogEngelsk
TidsskriftModern Pathology
Vol/bind21
Udgave nummer6
Sider (fra-til)700-707
Antal sider8
ISSN0893-3952
DOI
StatusUdgivet - 8. jun. 2008

Fingeraftryk

Prostatic Neoplasms
Messenger RNA
Neuroendocrine Cells
Paraffin
Real-Time Polymerase Chain Reaction
Neoplasms
RNA
Population

Citer dette

Rapa, I., Ceppi, P., Bollito, E., Rosas, R., Cappia, S., Bacillo, E., ... Volante, M. (2008). Human ASH1 expression in prostate cancer with neuroendocrine differentiation. Modern Pathology, 21(6), 700-707. https://doi.org/10.1038/modpathol.2008.39
Rapa, Ida ; Ceppi, Paolo ; Bollito, Enrico ; Rosas, Rosj ; Cappia, Susanna ; Bacillo, Elisa ; Porpiglia, Francesco ; Berruti, Alfredo ; Papotti, Mauro ; Volante, Marco. / Human ASH1 expression in prostate cancer with neuroendocrine differentiation. I: Modern Pathology. 2008 ; Bind 21, Nr. 6. s. 700-707.
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title = "Human ASH1 expression in prostate cancer with neuroendocrine differentiation",
abstract = "Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25{\%} of prostate cancers with neuroendocrine differentiation/ untreated, with a significant correlation with the extent of neuroendocrine features (P=0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P=0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivation-treated compared with untreated patients (P=0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two- to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.",
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Rapa, I, Ceppi, P, Bollito, E, Rosas, R, Cappia, S, Bacillo, E, Porpiglia, F, Berruti, A, Papotti, M & Volante, M 2008, 'Human ASH1 expression in prostate cancer with neuroendocrine differentiation', Modern Pathology, bind 21, nr. 6, s. 700-707. https://doi.org/10.1038/modpathol.2008.39

Human ASH1 expression in prostate cancer with neuroendocrine differentiation. / Rapa, Ida; Ceppi, Paolo; Bollito, Enrico; Rosas, Rosj; Cappia, Susanna; Bacillo, Elisa; Porpiglia, Francesco; Berruti, Alfredo; Papotti, Mauro; Volante, Marco.

I: Modern Pathology, Bind 21, Nr. 6, 08.06.2008, s. 700-707.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Human ASH1 expression in prostate cancer with neuroendocrine differentiation

AU - Rapa, Ida

AU - Ceppi, Paolo

AU - Bollito, Enrico

AU - Rosas, Rosj

AU - Cappia, Susanna

AU - Bacillo, Elisa

AU - Porpiglia, Francesco

AU - Berruti, Alfredo

AU - Papotti, Mauro

AU - Volante, Marco

PY - 2008/6/8

Y1 - 2008/6/8

N2 - Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25% of prostate cancers with neuroendocrine differentiation/ untreated, with a significant correlation with the extent of neuroendocrine features (P=0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P=0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivation-treated compared with untreated patients (P=0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two- to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.

AB - Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25% of prostate cancers with neuroendocrine differentiation/ untreated, with a significant correlation with the extent of neuroendocrine features (P=0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P=0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivation-treated compared with untreated patients (P=0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two- to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.

KW - hASH1

KW - Immunohistochemistry

KW - Neuroendocrine differentiation

KW - Prostate carcinoma

KW - Real-time PCR

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U2 - 10.1038/modpathol.2008.39

DO - 10.1038/modpathol.2008.39

M3 - Journal article

C2 - 18311112

AN - SCOPUS:44349099162

VL - 21

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EP - 707

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

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