High expression of thymidylate synthase is Associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy

Abstract

The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection

“…While the prognostic significance of poorly differentiated histology in gastric cancer is controversial, several studies have demonstrated that mixed type in Lauren's classification is associated with poor prognosis and other factors suggesting aggressive biologic behavior such as lymph node metastasis and advanced stage (Shiu et al, 1989;Kim et al, 1992;Carneiro et al, 1995;Macdonald et al, 1995;Yu et al, 1995;Setälä et al, 1996;Stelzner and Emmrich, 1997). Unlike the present results, other studies with gastric cancer tissue have failed to show any relationship between TS expression and tumour differentiation or Lauren's classification (Kuniyasu et al, 1998;Yeh et al, 1998;Suda et al, 1999). Considering the fact that mixed-type gastric cancer is associated with poor outcome of the patients, high TS expression may suggest intrinsic aggressive tumour behaviour.…”

“…High TS expression was associated with a high proportion of male gender in the current study. It was an unexpected finding considering the previous reports, and further studies would be necessary to find a possible explanation for such a result (Kuniyasu et al, 1998;Yeh et al, 1998;Suda et al, 1999). TS expression was not associated with other characteristics of prognostic significance such as primary tumour size, depth of tumour invasion, lymph node metastasis and postoperative pathologic stage.…”

“…In tumour cells, 5-FU is converted to 5-fluorodeoxyuridine monophosphate, which forms a tight-binding covalent complex with TS in the presence of folate cofactor 5, 10-methylene tetrahydrofolate (Pinedo and Peters, 1988). Several preclincal and clinical studies have demonstrated that increased expression of TS may be associated with 5-FU resistance in a variety of malignancies (Washtien, 1984;Johnston et al, 1992;Johnston et al, 1995;Lenz et al, 1996;Boku et al, 1998;Yeh, et al, 1998).…”

“…In gastric cancer, several studies have shown that TS expression has an inverse relationship with response to chemotherapy and survival in patients with locally advanced or metastatic disease receiving systemic chemotherapy with 5-FU-containing regimens (Johnston et al, 1995;Lenz et al, 1996;Boku et al, 1998;Yeh, et al, 1998). Moreover, TS expression also predicted poor disease-free and overall survival in a few reports that investigated gastric cancer patients treated with 5-FU-based adjuvant chemotherapy after surgical resection (Kuniyasu et al, 1998;Suda et al, 1999).…”

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

“…In fact, many previous studies have reported the intratumoural TS expression to be associated with tumour proliferation (Navalgund et al, 1980;Nakagawa et al, 2004), the responsiveness to 5-FU (Johnston et al, 1995;Yeh et al, 1998). In addition, the overexpression of TS is reported to be associated with a poor prognosis of many cancer patients treated with 5-FU, including NSCLCs (Huang et al, 2000) and gastrointestinal cancers (Lenz et al, 1996).…”