High nuclear expression of proteasome activator complex subunit 1 predicts poor survival in soft tissue leiomyosarcomas

Sha Lou, Arjen H. G. Cleven, Benjamin Balluff, Marieke de Graaff, Marie Kostine, Inge Briaire-de Bruijn, Liam A. McDonnell, Judith V. M. G. Bovee*

*Corresponding author for this work

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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.
Original languageEnglish
Article number17
JournalClinical Sarcoma Research
Volume6
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Proteasome activator complex subunit 1
  • Prognostic biomarker
  • Sarcoma
  • Leiomyosarcoma
  • Soft tissue sarcoma
  • Immunohistochemistry

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