Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.
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.


OBJECTIVE
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 (< or =5 cm) tumours (p = 0.02).


CONCLUSIONS
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.
Linder
N
N
Developmental and Reproductive Biology and Hospital for Children and Adolescents, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. nina.linder@hus.fi
Haglund
C
C
Lundin
M
M
Nordling
S
S
Ristimäki
A
A
Kokkola
A
A
Mrena
J
J
Wiksten
J-P
JP
Lundin
J
J
D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D014969:Xanthine Oxidase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D014969:Xanthine Oxidase