title: Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Oncology, Lund, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Nyström
authors.affiliation: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Oncology, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Jönsson
authors.affiliation: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Oncology, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Werner-Hartman
authors.affiliation: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Oncology, Lund, Sweden.|Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Nilbert
authors.affiliation: Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Oncology, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Carneiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012509:Sarcoma / Q000401:mortality / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D060726:Torso
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: MACROPHAGES; METASTASIS; SARCOMAS; STROMAL REACTION; TUMOUR MARKERS