Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis

Nicole Horrée, Paul J. Van Diest, Petra Van Der Groep, Daisy M D S Sie-Go, A. Peter M Heintz

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Hypoxia-inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF) in paraffin-embedded specimens of normal (n=17), premalignant (n=17) and endometrioid endometrial carcinoma (n=39) was explored by immunohistochemistry, in relation to microvessel density (MVD). Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61%) and carcinoma (87%), with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse) and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically). Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalCellular Oncology
Volume29
Issue number3
StatePublished - 2007
Externally publishedYes

Keywords

  • Carcinogenesis
  • Endometrium
  • HIF-1α
  • Hypoxia
  • Immunohistochemistry

ASJC Scopus subject areas

  • Cell Biology
  • Pathology and Forensic Medicine
  • Oncology

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