-Original-

Correlation between Clinical Pathologic Factors and Activity of 5-FU-Metabolizing Enzymes in Colorectal Cancer

Takeshi Yamada^1,2, Noritake Tanaka^1,2, Kimiyoshi Yokoi^1,2, Tomoko Seya^1,2, Yoshikazu Kanazawa^1,2, Michihiro Koizumi^1,2, Yoshiharu Ohaki³ and Takashi Tajiri¹

¹Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School
²Department of Surgery, Nippon Medical School, Chiba Hokusou Hospital
³Department of Pathology, Nippon Medical School, Chiba Hokusou Hospital

Introduction: Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) are initial key enzymes in the 5-fluorouracil (5-FU) metabolic pathway. The expression levels and activities of these three enzymes play important roles in the response of cancer patients to 5-FU-based chemotherapy.
Purpose: The purpose of this study was to investigate the relationship between the activities of 5-FU metabolic enzymes and clinicopathologic factors in colorectal cancer.
Methods: We measured the activities of OPRT, DPD, and TS in colorectal cancer tissues. We also investigated the correlations between the activities of these three enzymes and clinicopathologic factors (histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, and vascular invasion). We examined 100 patients with surgically resected colorectal cancer.
Results: Poorly differentiated adenocarcinoma showed significantly higher DPD activities than did moderately differentiated or well-differentiated adenocarcinoma. In patients with lymph-node metastasis, OPRT activity was significantly lower than in patients without lymph-node metastasis. No significant relation was found between TS activity and histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, or vascular invasion.
Conclusion: The response to 5-FU may be poor in patients with lymph-node metastasis, because of low OPRT activity, and in patients with poorly differentiated adenocarcinoma, because of high DPD activity.

J Nippon Med Sch 2008; 75: 23-27

Keywords
orotate phosphoribosyl transferase, dihydropyrimidine dehydrogenase, thymidylate synthase, colon cancer

Correspondence to
Takeshi Yamada, Department of Surgery, Nippon Medical School, Chiba Hokusou Hospital, 1715 Kamagari, Inba-mura, Inba-gun, Chiba 270-1694, Japan
y-tak@nms.ac.jp

Received, July 9, 2007
Accepted, November 6, 2007