Thymidine kinase in epithelial ovarian cancer: Relationship with the other pyrimidine pathway enzymes

Abstract

TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis. What roles TK may play in epithelial ovarian cancer and the relationships between TK and the other pyrimidine pathway enzymes remain unclear. We examined TKI gene expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69 samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16 benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK activities were determined by radioenzymatic assay. TKI gene expression, the ratio of TKI to TS gene expression, that of TKI to TP and that of TKI to DPD were significantly higher in epithelial ovarian cancer than in normal ovaries. In epithelial ovarian cancer, TKI gene expression correlated with cytosolic and serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene expression. Patients with high-TKI gene expression had a significantly poorer survival than those with low TKI gene expression. Combined analysis demonstrated that the relative risk of cancer death for tumors with high TKI, high TS and high TP gene expression was greater than that for tumors with high TKI gene expression alone. TKI gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. Combination therapy including TK inhibitor is a possible therapeutic intervention in patients with epithelial ovarian cancer. © 2002 Wiley-Liss, Inc.