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.