title: Hypoxia-inducible factor 1alpha expression in renal cell carcinoma analyzed by tissue microarray.
abstract: OBJECTIVE
  Angiogenesis is important for tumour progression and metastatic spread. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a major factor regulating a number of other angiogenic factors. Renal cell carcinoma (RCC) is a malignancy with a variable clinical course, partly attributable to specific genetic alterations of the different RCC types. We therefore analysed HIF-1alpha expression using immunohistochemistry and related the results to RCC type and clinicopathologic variables.
  
  
  METHODS
  We semiquantitatively analysed HIF-1alpha expression using immunohistological staining of a prepared tissue microarray. There were 216 patients including 176 conventional, 26 papillary, and 14 chromophobe RCCs.
  
  
  RESULTS
  The HIF-1alpha staining was found mainly in the cytoplasm. The tumours were subdivided into HIF-1alpha(LOW) and HIF-1alpha(HIGH) on the basis of staining intensity. HIF-1alpha expression between the RCC types did not differ. Patients with conventional RCC showed a trend (p=0.055) towards a prolonged survival for those with HIF-1alpha(HIGH)-staining versus HIF-1alpha(LOW)-staining tumors. In conventional RCC there were significant differences in HIF-1alpha expression in relation to TNM stage, nuclear grade, and vein invasion. In patients with papillary RCC, difference in HIF-1alpha expression was observed only for nuclear grade.
  
  
  CONCLUSIONS
  We studied HIF-1alpha expression in RCC using tissue microarray. In patients with conventional RCC, HIF-1alpha levels were significantly lower in locally aggressive tumors versus localized tumors, and patients with high HIF-1alpha levels tended to have a better prognosis. There seems to be a diverging regulation of angiogenesis between the different RCC types. Further studies of HIF and angiogenesis in RCC are encouraged.
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lidgren
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hedberg
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.forename: Torgny
authors.initials: T
authors.lastname: Rasmuson
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit