Cargando…

High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas

BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expressi...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramaglia, Maria, D’Angelo, Velia, Iannotta, Adriana, Di Pinto, Daniela, Pota, Elvira, Affinita, Maria Carmen, Donofrio, Vittoria, Errico, Maria Elena, Lombardi, Angela, Indolfi, Cristiana, Casale, Fiorina, Caraglia, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964052/
https://www.ncbi.nlm.nih.gov/pubmed/27471434
http://dx.doi.org/10.1186/s12935-016-0338-x
_version_ 1782445035580555264
author Ramaglia, Maria
D’Angelo, Velia
Iannotta, Adriana
Di Pinto, Daniela
Pota, Elvira
Affinita, Maria Carmen
Donofrio, Vittoria
Errico, Maria Elena
Lombardi, Angela
Indolfi, Cristiana
Casale, Fiorina
Caraglia, Michele
author_facet Ramaglia, Maria
D’Angelo, Velia
Iannotta, Adriana
Di Pinto, Daniela
Pota, Elvira
Affinita, Maria Carmen
Donofrio, Vittoria
Errico, Maria Elena
Lombardi, Angela
Indolfi, Cristiana
Casale, Fiorina
Caraglia, Michele
author_sort Ramaglia, Maria
collection PubMed
description BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expression of PRC2 proteins in pediatric soft tissue sarcoma (rhabdomyosarcoma, RMS and extraosseous Ewing sarcoma, EES) correlating them to the clinical outcome of the patients. METHODS: We analyzed PRC2 protein expression by quantitative real time PCR, western blotting and immunohistochemistry in 17 soft tissue sarcomas (11 RMS and 6 EES) enrolled at Paediatric Oncology Units of the Second University of Naples. Expression analysis was performed for EZH2, SUZ12 and EED. RESULTS: Enhancer of Zeste Drosophila Homologue 2 was expressed with a different degree in 60 % of samples. Interestingly, the magnitude of EZH2 up regulation was significantly higher in patients presenting lymph node and/or distant metastases at the diagnosis. Moreover, patients overexpressing EZH2 had a lower probability of survival compared to patients negative or with low EZH2 expression. CONCLUSIONS: Our study suggests that high EZH2 expression is associated to increased aggressiveness of the disease. Therefore, drugs that control its activity could be potentially used in the epigenetic target treatment of tumors with these alterations.
format Online
Article
Text
id pubmed-4964052
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-49640522016-07-29 High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas Ramaglia, Maria D’Angelo, Velia Iannotta, Adriana Di Pinto, Daniela Pota, Elvira Affinita, Maria Carmen Donofrio, Vittoria Errico, Maria Elena Lombardi, Angela Indolfi, Cristiana Casale, Fiorina Caraglia, Michele Cancer Cell Int Primary Research BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expression of PRC2 proteins in pediatric soft tissue sarcoma (rhabdomyosarcoma, RMS and extraosseous Ewing sarcoma, EES) correlating them to the clinical outcome of the patients. METHODS: We analyzed PRC2 protein expression by quantitative real time PCR, western blotting and immunohistochemistry in 17 soft tissue sarcomas (11 RMS and 6 EES) enrolled at Paediatric Oncology Units of the Second University of Naples. Expression analysis was performed for EZH2, SUZ12 and EED. RESULTS: Enhancer of Zeste Drosophila Homologue 2 was expressed with a different degree in 60 % of samples. Interestingly, the magnitude of EZH2 up regulation was significantly higher in patients presenting lymph node and/or distant metastases at the diagnosis. Moreover, patients overexpressing EZH2 had a lower probability of survival compared to patients negative or with low EZH2 expression. CONCLUSIONS: Our study suggests that high EZH2 expression is associated to increased aggressiveness of the disease. Therefore, drugs that control its activity could be potentially used in the epigenetic target treatment of tumors with these alterations. BioMed Central 2016-07-28 /pmc/articles/PMC4964052/ /pubmed/27471434 http://dx.doi.org/10.1186/s12935-016-0338-x Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Ramaglia, Maria
D’Angelo, Velia
Iannotta, Adriana
Di Pinto, Daniela
Pota, Elvira
Affinita, Maria Carmen
Donofrio, Vittoria
Errico, Maria Elena
Lombardi, Angela
Indolfi, Cristiana
Casale, Fiorina
Caraglia, Michele
High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title_full High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title_fullStr High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title_full_unstemmed High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title_short High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
title_sort high ezh2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964052/
https://www.ncbi.nlm.nih.gov/pubmed/27471434
http://dx.doi.org/10.1186/s12935-016-0338-x
work_keys_str_mv AT ramagliamaria highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT dangelovelia highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT iannottaadriana highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT dipintodaniela highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT potaelvira highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT affinitamariacarmen highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT donofriovittoria highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT erricomariaelena highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT lombardiangela highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT indolficristiana highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT casalefiorina highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas
AT caragliamichele highezh2expressioniscorrelatedtometastaticdiseaseinpediatricsofttissuesarcomas