Expression of dihydropyrimidine dehydrogenase in cancer cells but not in stromal cells predicts the efficacy of fluorouracil treatment in patients with gastric carcinoma.
BACKGROUND
It is not known whether immunohistochemical quantification of dihydropyrimidine dehydrogenase (DPD) in cancer cells, stromal mononuclear cells and normal glands predicts the efficacy of fluorouracil (FU) derivatives inpatients with T3 gastric adenocarcinoma.


METHODS
The levels of DPD in cancer cells, stromal cells and normal glands were measured immunohistochemically in 111 patients with T3 gastric carcinoma. Adjuvant chemotherapy with oral UFT (uracil/tegafur[4:1]) was administered to 95 patients for more than 1 year after surgery.


RESULTS
Forty-two (37.8%) patients demonstrated high DPD expression in the cytoplasm of their cancer cells. In patients with low DPD expression in cancer cells, the 5-year survival rates were 64.5% in patients given FU and 42.8% in those not given FU (p=0.014). Neither stromal cells nor normal glands affected the efficacy of FU treatment in relation to their DPD expression.


CONCLUSIONS
DPD expression in cancer cells but not in stromal cells could be a predictor of the efficacy of FU chemotherapy in patients with T3 gastric carcinoma.
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan. khisamit@k7.dion.ne.jp
Kazunori
K
Hisamitsu
Shunichi
S
Tsujitani
Kenichi
K
Yamaguchi
Kenji
K
Fukuda
Ichiro
I
Konishi
Nobuaki
N
Kaibara
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics; D017024:Chemotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D017154:Stromal Cells / Q000201:enzymology; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics; D013940:Thymidylate Synthase / Q000096:biosynthesis; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil