Expression of Thymidylate Synthase in Gastric Cancer

ABSTRACT

PURPOSE: 5-fluorouracil is one of the widely used chemotherapeutic agent whose metabolic product forms tight covalent binding complex with thymidylate synthase (TS) and thereby blocks the DNA synthesis process. Expression of TS has been studied as a mechanism of drug resistance and as a prognostic factor for various cancers. METHODS: The relation between TS expression in surgically resected specimens and clinicopathologic features was examined in 62 patients with gastric cancer. Immuno histochemical demonstration of the protein was achieved using an anti-TS monoclonal antibody. RESULTS: In Lauren's classification, TS expressions of the intestinal type and the diffuse type were 21.93% and 14.96% respectively (P=0.02). And TS expression in a group with lymphatic invasion was higher (26.15%) than that in a group without lymphatic invasion (16.15%)(P=0.0001). There were no significant differences between the TS expressions associated with other clinicopathologic features (P>0.05). CONCLUSION: For the purpose of assessing the applicability of TS expression as a prognostic factor and as a mechanism for drug resistance, assessment of TS expression must be standardized. Although direct correlations between TS expression and other clinicopathologic features were found only in Lauren's classification and lymphatic invasion, further investigations of the relation between TS expression and drug resistance of 5-FU must be continued to provide data for choosing chemotherapuetic agents for use in patients with gastric cancer.