Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy.
OBJECTIVE
We investigated whether the intensity of thymidylate synthase (TS) staining in tissue samples obtained from gastric cancer (GC) patients undergoing gastrectomy could predict response to 5-FU-based adjuvant chemotherapy after gastrectomy.


METHODS
Clinicopathological features of 124 patients with histologically proven GC who underwent radical gastrectomy were retrospectively reviewed. Tissue samples obtained from these patients were immunohistochemically stained for assessing TS expression. We arbitrarily classified the TS staining results as low (<20% cytoplasmic immunostaining) and high (> or =20% cytoplasmic immunostaining) TS expression.


RESULTS
The clinicopathological features of the low TS expression group patients were typically similar to those of the high TS expression group patients. However, multivariate forward stepwise logistic regression analysis revealed that low TS expression was independently associated with females and responders to 5-FU-based adjuvant chemotherapy. The median follow-up duration for the 124 GC patients who had undergone curative resection was 41.3 months. The GC patients who showed poor tumor differentiation and high TS expression had short disease-free survival (DFS) and overall survival (OS).


CONCLUSIONS
Low TS expression is significantly associated with female GC patients and responders to 5-FU-based adjuvant chemotherapy. It predicts longer DFS and OS in selected GC patients treated with 5-FU-based adjuvant chemotherapy after curative resection. The results suggest that prospective assessment of TS staining intensity in tissue samples obtained from GC patients undergoing gastrectomy would be useful to predict the patients who would be benefited from 5-FU-based adjuvant chemotherapy after gastrectomy.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, Republic of China. ycn@adm.cgmh.org.tw
Jung
Shih-Ming
SM
Chen
Tsung-Wen
TW
Hwang
Tsann-Long
TL
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005472:Fluorouracil / Q000627:therapeutic use*; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil