title: Decreased xanthine oxidoreductase (XOR) is associated with a worse prognosis in patients with serous ovarian carcinoma.
abstract: OBJECTIVE
  Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. In the human cancers previously studied, down-regulated XOR identifies patients with unfavorable prognosis. We assessed the clinical relevance of XOR expression in serous ovarian cancer.
  
  
  METHODS
  XOR protein was determined in tissue microarrays from 474 patients with serous ovarian cancer and analyzed with respect to clinical parameters and survival.
  
  
  RESULTS
  XOR was down regulated in 64% of the tumors as compared to the corresponding normal tissue. Decreased XOR was associated with a poorly differentiated tumor and an abnormal p53 expression, but not with age at diagnosis, FIGO stage, Ki-67 or tumor size. XOR expression was associated with outcome, and the five year ovarian cancer specific survival in patients with strong XOR expression was 59% compared to 44% in those with moderate (hazard ratio, HR; 1.44; P=0.0083) and 26% in patients with lack of XOR (HR, 2.07; P=0.0003). This was also true in patients whose tumors were highly differentiated (HR, 3.67; P=0.008) and in patients with a small (<1cm) residual tumor (HR, 2.62; P=0.017), and in patients whose tumors show a low Ki-67 protein expression (HR, 3.79; P<0.0001). In multivariate survival analysis, absence of XOR emerged as an independent prognostic factor (HR, 1.82; P=0.015).
  
  
  CONCLUSIONS
  Decreased XOR is associated with poorer prognosis in patients with serous ovarian cancer especially in those with an otherwise more favorable prognostic profile.
authors: FIMM, Institute for Molecular Medicine Finland, P.O. Box 20, FI-00014 University of Helsinki, Finland. nina.linder@helsinki.fi
authors: Nina
authors: N
authors: Linder
authors: Ralf
authors: R
authors: Bützow
authors: Heini
authors: H
authors: Lassus
authors: Mikael
authors: M
authors: Lundin
authors: Johan
authors: J
authors: Lundin
mesh_terms: D018284:Cystadenocarcinoma, Serous / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D014968:Xanthine Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014968:Xanthine Dehydrogenase