5-FU sensitivity and thymidylate synthase in gastric cancer

The relationship of 5-FU-sensitivity to thymidylate synthase (TS) was investigated in a total of 82 gastric cancers of stage III or IV. The sensitivity test was done by Histoculture Drug Response Assay and TS expression was stained immunohistochemically using anti-TS antibody. Sensitivity to 5-FU of more than 50% of the inhibitory index (high sensitivity) was observed in 28.1% of the materials, less than 50% (low sensitivity) in 71.9% and less than 20% in 50.0%. The expression of TS was found in 25.6% of the patients. The incidence of positive TS expression was 34.5% in the high sensitivity group, against 22.0% in the low sensitivity group, with no statistical difference between them. No particular relationship was found between 5-FU-sensitivity group and TS expression rate when the tumor-histology was divided into high and low differentiation. In the present study, the ratio of patients negative for TS among the high 5-FU-sensitivity group both was 65.2%, both of which have been reported as producing high survival rates. In contrast, the ratio of patients positive for TS in the low 5-FU-sensitivity group was 22.0%. From these results, TS is considered to be responsible for approximately 40-50% of either high or low 5-FU-sensitivity, respectively, when the lower TS expression in the present study was taken into consideration and corrected.