Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer

5-Fluorouracil (5FU)-based therapy is given to patients with advanced color ectal cancer and as adjuvant treatment. Thymidylate synthase (TS) is the ta rget for 5FU, and may have a prognostic role for the outcome of 5FU-based t herapy together with proliferation markers such as p53 and Ki67, Thymidine phosphorylase (TP, also known as platelet-derived endothelial cell growth f actor) may be of importance both in the 5FU drug activation pathway and in tumor angiogenesis, similar to vascular endothelial growth factor (VEGF), T S and TP levels were determined biochemically in fresh-frozen tumor specime ns of 32 untreated patients with colorectal cancer, whereas in paraffin-emb edded tissue samples, immunohistochemistry was performed for TS, TP, and ad ditional prognostic markers such as p53, Ki67, and VEGF as well as microves sel density. All factors were correlated with patient characteristics such as age, gender, Dukes' stage, angio-invasion, and differentiation grade. TS and TP as measured by various assays were correlated with overall and dise ase-free survival in this patient group. TP enzyme activity and protein exp ression correlated with each other. A significant correlation was found bet ween TP enzyme activity and 5-fluoro-2'-deoxyuridine-5'-monophosphate bindi ng activity. VEGF expression correlated significantly with TP immunostainin g and Ki67 index. Survival analysis revealed a significant relation of TS l evels to the overall survival in this small patient group and a significant correlation be-tween TP activity and disease-free survival. TS and TP both were of prognostic significance in these patients with colorectal cancer. The interesting relationship of TS and TP with angiogenesis and proliferati on needs further investigation.