Relation between thymidylate synthase expression and survival in colon carcinoma, and determination of appropriate application of 5-fluorouracil by immunohistochemical method.
BACKGROUND
Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied.


METHODS
Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup.


RESULTS
Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439).


CONCLUSIONS
TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.
Takenoue
T
T
Department of Surgical Oncology, University of Tokyo, Japan. takenoue-1su@h.u-tokyo.ac.jp
Nagawa
H
H
Matsuda
K
K
Fujii
S
S
Nita
M E
ME
Hatano
K
K
Kitayama
J
J
Tsuruo
T
T
Muto
T
T
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil