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Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer
  1. N Linder1,
  2. C Haglund2,
  3. M Lundin3,
  4. S Nordling5,
  5. A Ristimäki4,
  6. A Kokkola2,
  7. J Mrena2,
  8. J-P Wiksten3,
  9. J Lundin3
  1. 1Developmental and Reproductive Biology and Hospital for Children and Adolescents, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
  2. 2Department of Surgery, Helsinki University Central Hospital, Helsinki
  3. 3Department of Oncology, Helsinki University Central Hospital
  4. 4Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki
  5. 5Department of Pathology, University of Helsinki
  1. Correspondence to:
    N Linder
    Research Program for Developmental and Reproductive Biology, Room B524b, Biomedicum Helsinki, University of Helsinki, PO Box 63 (Haartmaninkatu 8), 00014 Helsinki, Finland; nina.linder{at}hus.fi

Abstract

Background: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR.

Aim: To assess the clinical relevance of XOR expression in gastric cancer.

Methods: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed.

Results: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I–II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (⩽5 cm) tumours (p = 0.02).

Conclusion: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

  • COX-2, cyclooxygenase-2
  • SPF, S-phase fraction
  • XOR, xanthine oxidoreductase

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Footnotes

  • Competing interests: None declared.

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