title: Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.
abstract: The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Mitsuyama
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Anan
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ohkuma
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Eto
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
keywords: S-1; adjuvant chemotherapy; colorectal cancer; thymidine phosphorylase