The role of thymidylate synthase levels in the prognosis and the treatment of patients with colorectal cancer.

Inhibition of Thymidylate Synthase (TS) by the 5-Fluorouracil (5Fu) active metabolite Fluoro-deoxy-uridine-monophosphate (FdUMP) is considered to be the main mechanism of action of 5Fu. TS level from tumors and normal mucosa of 62 untreated patients who underwent surgery for primary colorectal adenocarcinoma was performed. The aim of this study was to evaluate the possibility of considering the TS level as a prognostic factor of the disease. A large variation in the level of the enzyme was found among tumors. Our data demonstrate that there is no association with age, sex, and tumor size; however there are significant relationships between TS levels and staging and histological grading. In fact the TS values are higher in Dukes' A and in G1 than in Dukes' D and G3 tumors (p < 0.05). Another significant association has been found between the TS level and tumor site: pts with right colon neoplasias had higher TS levels than pts with left and rectum ones. An interesting trend was found between the TS levels and survival parameters. Pts who had lower TS levels had a significantly increased risk of death (p < 0.05) over pts with a higher outcome. Our data support the hypothesis that a high TS level is a favourable prognostic factor in human untreated colorectal carcinomas according to our previous preliminary data (1).