Objective: To study the relationship between the expression of thymidylate synthase (TS) gene and the prognosis of colorectal carcinoma and between the TS expression and the effect of 5-fluorouracil (5-Fu) on advanced colorectal carcinoma.
Methods: 134 formalin-fixed and paraffin-embedded specimens of colorectal carcinoma obtained during operation from 134 patients, 65 males and 69 females, aged 34 approximately 76 with an average age of 51 +/- 11, 16 with differentiated carcinoma and 118 with undifferentiated carcinoma, 4 with infiltration into mucous layer, 21 into submucous layer, 100 into muscular layer, and 5 into serous layer, 25 without lymphatic metastasis and 109 with lymphatic metastasis, 4 in stage IB, 15 in stage II, 90 in stage IIIA, and 27 in stage IIIB by Dukes staging, underwent immunohistochemistry (ABC methods) to determine the expression of TS. After operation all patients received chemotherapy with leucovorin and 5-Fu for 4 approximately 6 periods and were followed up for 9 approximately 72 months.
Results: Eighty-two specimens showed high TS expression and 52 showed low TS expression. The grade of TS expression was significantly correlated with four clinicopathologic variables: histological type, depth of invasion, lymphatic metastasis, and Dukes' stage (all P < 0.001). The 5-year survival rate for the low TS group was 57.69%, significantly lower than that of the high TS group (21.95%, P < 0.001). Multivariate analysis revealed that three variables (histological type, depth of infiltration, and TS grade) independently contributed to the survival rate (all P < 0.05), especially the TS grade (all P < 0.0001). The relative hazard ratio of TS grade was 1.241.
Conclusion: The expression of TS is one of the important prognosis indicators of colorectal carcinoma. It is also a relatively reliable indicator of whether 5-Fu should be used in the treatment of patients with colorectal carcinoma.