THYMIDYLATE SYNTHASE LEVEL AND DNA-PLOIDY PATTERN AS POSSIBLE PROGNOSTIC FACTORS IN HUMAN COLORECTAL-CANCER - A PRELIMINARY-STUDY

5-Fluorouracil is the drug chosen for the treatment of patients with a dvanced colorectal carcinoma; its major site of action is thymidylate synthase (TS), resulting in pronounced and prolonged inhibition of DNA synthesis: The aim of this study was to evaluate the possibility of c onsidering TS level in human colorectal carcinomas of previously untre ated patients (pts) as a prognostic factor. Our data demonstrate that there is no association with age, sex, tumor site and tumor size; howe ver, there is a relationship between TS levels and staging in fact, th e TS values are higher (P < 0.05) in Dukes-A tumors than in the others . A significant association was also found between the TS levels and s urvival parameters: in fact pts with longer disease-free and overall s urvivals had a significantly increased TS level compared to pts with a poorer outcome (P < 0.05). Moreover, pts with DNA-aneuploid tumors ha d lower TS level (median = 0.044 pmol/mg protein) than diploid pts who had higher TS level (median 0.093 pmol/mg protein); however the diffe rence is not significant. Our result are based on preliminary data; ho wever, they seem to support the hypothesis that a high TS level is a f avourable prognostic factor in human colorectal carcinoma.