Thymidylate Synthase Expression in Colorectal Cancer: A Prognostic and Predictive Marker of Benefit From Adjuvant Fluorouracil-Based Chemotherapy

PURPOSE: We studied the prognostic value of thymidylate synthase (TS) expression in primary colorectal cancer (CRC) and the role of TS expression as a predictor of chemotherapeutic benefit in patients treated with adjuvant chemotherapy. PATIENTS AND METHODS: TS expression was immunohistochemically assessed on tumor sections from 862 patients with CRC Dukes’ stages B and C enrolled onto randomized trials evaluating fluorouracil (5-FU)-based adjuvant chemotherapy. RESULTS: TS expression was an independent prognostic factor for disease-free (P = .05) and overall survival (P = .05). In the subgroup treated with surgery alone, TS was an independent prognostic factor for disease-free (P < .001) and overall survival (P = .001), whereas this was not the case in the subgroup of adjuvantly treated patients. Patients whose tumors expressed high TS levels had a tendency to improved outcome after adjuvant therapy (not significant). The group whose tumors expressed the highest TS grade, grade 3 (34% of the patients), h...