title: High nuclear expression of proteasome activator complex subunit 1 predicts poor survival in soft tissue leiomyosarcomas.
abstract: BACKGROUND
  Previous studies on high grade sarcomas using mass spectrometry imaging showed proteasome activator complex subunit 1 (PSME1) to be associated with poor survival in soft tissue sarcoma patients. PSME1 is involved in immunoproteasome assembly for generating tumor antigens presented by MHC class I molecules. In this study, we aimed to validate PSME1 as a prognostic biomarker in an independent and larger series of soft tissue sarcomas by immunohistochemistry.
  
  
  METHODS
  Tissue microarrays containing leiomyosarcomas (n = 34), myxofibrosarcomas (n = 14), undifferentiated pleomorphic sarcomas (n = 15), undifferentiated spindle cell sarcomas (n = 4), pleomorphic liposarcomas (n = 4), pleomorphic rhabdomyosarcomas (n = 2), and uterine leiomyomas (n = 7) were analyzed for protein expression of PSME1 using immunohistochemistry. Survival times were compared between high and low expression groups using Kaplan-Meier analysis. Cox regression models as multivariate analysis were performed to evaluate whether the associations were independent of other important clinical covariates.
  
  
  RESULTS
  PSME1 expression was variable among soft tissue sarcomas. In leiomyosarcomas, high expression was associated with overall poor survival (p = 0.034), decreased metastasis-free survival (p = 0.002) and lower event-free survival (p = 0.007). Using multivariate analysis, the association between PSME1 expression and metastasis-free survival was still significant (p = 0.025) and independent of the histological grade.
  
  
  CONCLUSIONS
  High expression of PSME1 is associated with poor metastasis-free survival in soft tissue leiomyosarcoma patients, and might be used as an independent prognostic biomarker.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, Postzone L1-Q, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Sha
authors.initials: S
authors.lastname: Lou
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjen H G
authors.initials: AH
authors.lastname: Cleven
authors.affiliation: Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: de Graaff
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marie
authors.initials: M
authors.lastname: Kostine
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Briaire-de Bruijn
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, Postzone L1-Q, Postbus 9600, 2300 RC Leiden, The Netherlands ; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands ; Fondazione Pisana per la Scienza ONLUS, Pisa, Italy.
authors.forename: Liam A
authors.initials: LA
authors.lastname: McDonnell
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Judith V M G
authors.identifier: 0000-0003-1155-0481
authors.initials: JV
authors.lastname: Bovée
keywords: Immunohistochemistry; Leiomyosarcoma; Prognostic biomarker; Proteasome activator complex subunit 1; Sarcoma; Soft tissue sarcoma