Prognostic and Predictive Value of Thymidylate Synthase Expression in Primary Colorectal Cancer

Aim: To investigate thymidylate synthase (TS) expression in primary colorectal cancer (CRC) as a prognostic and predictive marker of benefit for adjuvant chemotherapy. Patients and Methods: TS expression was immuno0-histochemically (IHC) assessed oil tumors from 1,389 patients with stage II and III CRC randomly assigned to either surgery alone or surgery plus 5-fluorouracil (5-FU)-based adjuvant chemotherapy. Results: In the subgroup treated with surgery alone (n=708), TS expression was prognostic using the classification of TS 0-1 versus 2-3 (p=0.045) as well as TS classified as 0-2 versus 3 (p=0.002). A high TS expression was associated with a shorter overall survival. Among patients with TS grade 3 (n=460), the subgroup treated with adjuvant chemotherapy had a significant longer OS (p=0.005). Conclusion: In this study TS, immunohistochemistry assessed, is a prognostic factor in CRC patients treated with surgery alone. Patients with the highest level of TS expression (grade 3) had all improved clinical outcome following adjuvant 5-FU-based chemotherapy.