Thymidylate synthase is a predictor of chemosensitivity to different 5-fluorouracil regimens in primary colorectal cancer.

B41

Purpose: To identify the good marker for the help of adjuvant 5-fluorouracil (5-FU) therapy to primary colorectal cancer by using different 5-FU regimens. Patients and methods: Primary colorectal cancer tissue from 24 patients were investigated to evaluate the relationship between the mRNA expression level of several 5-fluorouracil (5-FU)-related metabolic enzymes (thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase(TP)) and chemosensitivity to 2 different 5-FU regimens (1. 5-FU concentration 1.0 μg/mL, 24 h exposure 2. 5-FU concentration 0.3 μg/mL, 144 h exposure). Chemosensitivity and mRNA expression levels were measured by using collagen gel droplet embedded culture drug sensitivity tests and real-time quantitative reverse transcription-polymerase chain reaction. Results: The TS mRNA expression level were significantly higher in 5-FU resistant group (T/C > 60%) compared with 5-FU sensitive one (T/C < 60%) in both 5-FU regimens (1. 5.03 ∓ 0.92 v.s. 1.58 ∓ 0.76, p < 0.01, 2. 4.88 ∓ 0.91 v.s. 0.96 ∓ 0.20,p < 0.001). The group with higher TS mRNA expression level (> the average, 3.83) were more resistant to both 5-FU regimens than the one with lower TS mRNA ( < 3.83) (1. T/C=80% vs 66%, p=0.09, 2. T/C=89% vs 64%, p < 0.005).The TS mRNA expression level inversely correlated with the sensitivity to latter 5-FU regimen (R = 0.577, p < 0.01). There were no relationships between chemosensitivity to 5-FU and mRNA expression level of DPD and TP. Conclusions: TS mRNA expression level might be a good predictor of chemosensitivity to 5-FU in primary colorectal cancer, especially low dose and long duration regimen such as oral adjuvant treatment.