title: High EZH2 expression is correlated to metastatic disease in pediatric soft tissue sarcomas.
abstract: 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.
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ramaglia
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Velia
authors.initials: V
authors.lastname: D'Angelo
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Iannotta
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Pinto
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Pota
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Affinita
authors.affiliation: Pediatric Pathology Unit, Pausilipon Hospital, Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Donofrio
authors.affiliation: Pediatric Pathology Unit, Pausilipon Hospital, Naples, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Errico
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardi
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Indolfi
authors.affiliation: Department of Woman, Child and General and Specialized Surgery, Pediatric Oncology Unit, Second University of Naples, Via L. De Crecchio, 2, 80138 Naples, Italy.
authors.forename: Fiorina
authors.initials: F
authors.lastname: Casale
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
keywords: EZH2; PRC2; Pediatric sarcoma; Polycomb proteins