Xanthine oxidoreductase and chemosensitivity in non-small cell lung cancer

Abstract

11077 Background: Xanthine oxidoreductase (XOR) is an enzyme involved in the degradation of purines into uric acid and reactive oxygen species and activation of the MAP kinase pathway involved in apoptosis. Decreased XOR expression was shown in recent studies to be associated with more aggressive disease in breast (Linder et al. Clin Cancer Res. 2005;11:4372–4381) and gastric cancers (Linder et al. J Clin Pathol. 2006;59:965–971). The goal of our study was to show that decreased XOR expression was associated with decreased survival in non-small cell lung cancer (NSCLC). Methods: Tissue specimens from 82 patients (pts) were stained using a XOR specific antibody (36 male and 46 female, age range from 40 to 92 years). These included 41 adenocarcinoma, 31 squamous cell, 8 poorly/moderately differentiated, and 2 bronchioloalveolar. XOR staining intensity was measured on a scale of 0 through 4 (0 being no staining). XOR intensity was correlated with clinical characteristics and outcomes using log rank and COX PH regression analysis. Results: Of the 82 pts, 34 received adjuvant chemo, and of these, 15 specimens had low XOR intensity (0–1). These 15 pts received adjuvant chemo and had a median survival of 543 days. In comparison, 19 of the 34 pts receiving adjuvant chemo had specimens with high XOR intensity (2–4). Their median survival was significantly longer at 2,023 days (p=0.007, hazard ratio=0.33). Conclusions: Although we had a small sample size, in our retrospective study, we found that pts who received adjuvant chemo had a longer survival if their tumors expressed high levels of XOR. XOR could be a potential predictor for responsiveness to adjuvant chemo in patients with NSCLC. Pts with decreased XOR may be less responsive to chemo and thus be able to avoid a toxic treatment if it is not significantly beneficial. [Table: see text] No significant financial relationships to disclose.