title: Overexpression of hypoxia-inducible factor-1alpha predicts an unfavorable outcome in urothelial carcinoma of the upper urinary tract.
abstract: OBJECTIVE
  Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in cell hypoxia adaptation. Overexpression of HIF-1alpha subunit has been reported to be involved in the carcinogenesis, progression and metastasis of many human cancers. We evaluated the clinical significance of HIF-1alpha expression in urothelial carcinoma (UC) of the upper urinary tract.
  
  
  METHODS
  Ninety-eight cases (mean age = 63.5 +/- 11.7, range = 23-84 years) of renal pelvic or ureter UC were included in the present study. Those who had distant metastasis at diagnosis, other cancer, urolithiasis, incomplete clinical information or had received radiotherapy or chemotherapy before surgery were excluded. Nuclear HIF-1alpha expression were evaluated by immunohistochemistry staining on a paraffin-embedded section of the tumor and non-malignant upper urinary tract specimens and scored by two qualified pathologists. Clinical data were collected retrospectively.
  
  
  RESULTS
  Positive HIF-1alpha expression was found in 65 (66.3%) of the cancer specimens. No HIF-1alpha expression was found in normal urothelial specimens. Tumor HIF-1alpha expression score was significantly correlated with tumor T stage (P < 0.001), N stage (P < 0.001) and grade (P = 0.004). Tumor necrosis was associated with high tumor T stage (P < 0.001), N stage (P = 0.002) and grade (P < 0.001). Higher HIF-1alpha score (negative vs 3-5 vs 6-7) was a significant predictor for cancer-specific survival (Cox regression hazard ratio = 2.23, P = 0.004), and tumor recurrence (Cox regression hazard ratio = 1.58, P = 0.036).
  
  
  CONCLUSIONS
  Our findings indicate that HIF-1alpha immunostaining may have an important role in predicting prognosis in upper urinary tract urothelial carcinoma.
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Hung-Lung
authors.initials: HL
authors.lastname: Ke
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Wei
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Ching-Chia
authors.initials: CC
authors.lastname: Li
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Chun-Hsiung
authors.initials: CH
authors.lastname: Huang
authors.forename: Wen-Jeng
authors.initials: WJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000401:mortality
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit