title: Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct early renal cortical tumors.
abstract: OBJECTIVE
  The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in genetically distinct early renal cortical tumors.
  
  
  METHODS
  Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells.
  
  
  RESULTS
  Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2alpha.
  
  
  CONCLUSIONS
  Differential patterns of HIF-1alpha and HIF-2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha vs HIF-2alpha is suggested by the distinct subcellular localization pattern of HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1107, USA.
authors.forename: Chong M
authors.initials: CM
authors.lastname: Kim
authors.forename: Cathy
authors.initials: C
authors.lastname: Vocke
authors.forename: Carlos
authors.initials: C
authors.lastname: Torres-Cabala
authors.forename: Youfeng
authors.initials: Y
authors.lastname: Yang
authors.forename: Laura
authors.initials: L
authors.lastname: Schmidt
authors.forename: McClellan
authors.initials: M
authors.lastname: Walther
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D007672:Kidney Cortex; D007680:Kidney Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1