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Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall
  1. H Nyström1,
  2. M Jönsson2,
  3. L Werner-Hartman2,
  4. M Nilbert2,3,
  5. A Carneiro1
  1. 1 Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Oncology, Lund, Sweden
  2. 2 Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Oncology, Lund, Sweden
  3. 3 Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark
  1. Correspondence to Dr Helena NyströmDivision of Oncology, Institute of Clinical Sciences, Skane University Hospital, Lund 221 85, Sweden; Helena.Nystrom{at}


Background and aim Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma.

Method We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)α using immunohistochemical staining and assessed microvessel density using CD31 in 73 high-grade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival.

Results Expression of HIF-1α was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant in this series.

Conclusions There is increasing evidence for the prognostic role of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF-1α expression represents a candidate prognostic biomarker for clinical application in high-grade leiomyosarcoma and undifferentiated pleomorphic sarcoma.


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  • Handling editor Cheok Soon Lee.

  • Contributors AC, MN and HN were responsible for study design. HN, AC, MN and MJ performed immunohistochemical evaluations. HN, LW-H, AC and MN were involved in data analysis and interpretation of data. HN, AC and MN were responsible for drafting the manuscript. MJ and LW-H revised the manuscript critically for important intellectual content.

  • Funding This study was financially supported by the Swedish Cancer Fund, the ALF Funds at Lund University, the Nilsson Cancer Fund and the Kamprad Cancer Fund. Immunohistochemical stainings for CD16, CD163, CSF-1 were kindly performed by I Espinosa, Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain and M Van de Rijn, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA

  • Competing interests None declared.

  • Ethics approval Lund Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.