title: Increased angiogenesis is associated with a 32-gene expression signature and 6p21 amplification in aggressive endometrial cancer.
abstract: BACKGROUND
  Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel proliferation is associated with gene expression profiles or copy number alterations in endometrial cancer.
  
  
  METHODS
  A prospective series of endometrial carcinomas was studied for angiogenesis markers, gene expression profiles, and gene copy number data. For validation, an independent series of endometrial carcinomas as well as an external cohort of endometrial cancer patients were examined by gene expression microarrays.
  
  
  RESULTS
  Increased microvessel proliferation (MVP) was associated with aggressive tumor features and reduced survival, and a 32-gene expression signature was found to separate tumors with high versus low MVP. An increased 32-gene signature score was confirmed to associate with high-grade tumor features and reduced survival by independent cohorts. Copy number studies revealed that amplification of the 6p21 region was significantly associated with MVP, a high 32-gene score, as well as reduced survival.
  
  
  CONCLUSIONS
  Increased MVP was significantly associated with aggressive endometrial cancer and reduced survival. Integrated analyses demonstrated significant associations between increased vascular proliferation, amplification of the 6p21 region, VEGF-A mRNA expression, and the 32-gene angiogenesis signature. Our findings indicate amplification of 6p21 as a possible driver of tumor vascular proliferation in endometrial cancer.
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Ingunn M
authors: IM
authors: Stefansson
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
authors: Maria
authors: M
authors: Raeder
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Elisabeth
authors: E
authors: Wik
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Monica
authors: M
authors: Mannelqvist
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
authors: Kanthida
authors: K
authors: Kusonmano
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Gøril
authors: G
authors: Knutsvik
authors: Department of Radiology, Haukeland University Hospital, Bergen, Norway.|Section for Radiology, University of Bergen, Bergen, Norway.
authors: Ingfrid
authors: I
authors: Haldorsen
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
authors: Jone
authors: J
authors: Trovik
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors: Anne M
authors: AM
authors: Øyan
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors: Karl-H
authors: KH
authors: Kalland
authors: Department of Obstetrics and Gynaecology, Women and Children's Division, Oslo University Hospital, University of Oslo, Norway.
authors: Anne Cathrine
authors: AC
authors: Staff
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
authors: Helga B
authors: HB
authors: Salvesen
authors: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Lars A
authors: LA
authors: Akslen
mesh_terms: D002896:Chromosomes, Human, Pair 6; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D059467:Transcriptome
keywords: angiogenesis; endometrial cancer; gene expression signature; prognosis