Prognostic Significance of the Thymidylate Biosynthetic Enzymes in Human Colorectal Tumors

Abstract

The aim of the present study was to determine the relative intratumoral activity of two pyrimidine biosynthetic enzymes, i.e. thymidylate synthase (TS) and thymidine kinase (TK), in human colorectal cancers to compare their possible relationship with demographic and pathologic characteristics of the patients and their tumors, and moreover to evaluate their predictive significance regarding 5-fluorouracil (5-FU) sensitivity and the overall survival of patients, respectively. TS and TK levels were significantly increased in the tumor compared to peritumoral tissue. However, no significant relationship between TS/TK activity and demographic features of the patients or pathologic characteristics of their tumors could be demonstrated. Kaplan-Meier analysis showed that the overall survival of patients with low TS activity was significantly longer (p < 0.012) compared to those with high TS activity. Such a difference could not be demonstrated between patients with high or low TK activity; however, combined evaluation of the two parameters proved that TK may contribute to the more precise assessment of disease prognosis, and it may further influence treatment decisions, i.e. the selection of patients for adjuvant therapy with 5-FU and folinic acid. Multivariate analysis showed that among the variables tested, beside Dukes’ stage, TS and TK activities were significant prognostic factors for the overall survival of colorectal cancer patients.