Expression of Dihydropyrimidine Dehydrogenase in Cancer Cells but Not in Stromal Cells Predicts the Efficacy of Fluorouracil Treatment in Patients with Gastric Carcinoma

• Published in: Anticancer research Vol. 24; no. 4; pp. 2495 - 2501
• Main Authors: HISAMITSU, Kazunori, TSUJITANI, Shunichi, YAMAGUCHI, Kenichi, FUKUDA, Kenji, KONISHI, Ichiro, KAIBARA, Nobuaki
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.07.2004
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Biological and medical sciences; Chemotherapy, Adjuvant; Dihydrouracil Dehydrogenase (NADP) - biosynthesis; Dihydrouracil Dehydrogenase (NADP) - metabolism; Female; Fluorouracil - pharmacokinetics; Fluorouracil - therapeutic use; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Neoplasm Staging; Stomach Neoplasms - drug therapy; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Stromal Cells - enzymology; Tegafur - administration & dosage; Tegafur - pharmacokinetics; Thymidylate Synthase - biosynthesis; Tumors; Uracil - administration & dosage; Uracil - pharmacokinetics; Antineoplastic agent; adjuvant chemotherapy; dihydropyrimidine dehydrogenase; Carcinoma; 5-Fluorouracil; Dehydrogenase; Cancerology; Adjuvant; Stromal cell; gastric carcinoma; Tumor cell; Fluorouracil; Human; Postoperative; Stomach; Digestive system; Enzyme; Transferases; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Survival; Chemotherapy; Treatment; Antimetabolic; Methyltransferases; postoperative survival; Pyrimidine derivatives; Oxidoreductases
• ISSN: 0250-7005; 1791-7530

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 in patients with T3 gastric adenocarcinoma. Materials and 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. Conclusion: 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.