Correlation between clinical pathologic factors and activity of 5-FU-metabolizing enzymes in colorectal cancer.
BACKGROUND
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Yamada
Takeshi
T
Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School, Japan. y-tak@nms.ac.jp
Tanaka
Noritake
N
Yokoi
Kimiyoshi
K
Seya
Tomoko
T
Kanazawa
Yoshikazu
Y
Koizumi
Michihiro
M
Ohaki
Yoshiharu
Y
Tajiri
Takashi
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil