[Correlation between clinical pathophysiologic factors and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer].
We measured the activity of orotate phosphoribosyl transferase (OPRT), the amount of thymidylate synthase (TS) enzyme, and the activity of dihydropyrimidine dehydrogenase (DPD) for individual tissue types in order to study the contribution of these substances to the effects of the pyrimidine fluoride anticancer drug 5-fluorouracil (5-FU). We also studied the correlation between these 3 enzymes and clinical pathophysiologic characteristics (age, sex, extent of tumor invasion, extent of metastasis to the lymph nodes, lymphatic invasion and the venous invasion of the colorectal wall). Sixty-eight patients with colorectal carcinoma who had undergone surgical resection in our department were studied. There was a significant (p < 0.01) elevation of OPRT activity in the tumor tissue compared with regions of normal tissue. OPRT activity levels in the tumor tissue were lowest in patients with mucinous carcinoma while TS enzyme levels showed the highest activity in tumor tissue in poorly differentiated adenocarcinoma. DPD also showed high activity levels in tumor tissue in poorly differentiated adenocarcinoma and mucinous carcinoma. It is possible that the expression of enzymes with respect to the antitumor effects of 5-FU is a factor contributing to the poor prognosis for patients with poorly differentiated adenocarcinoma and mucinous carcinoma. In the present study of clinical pathophysiologic characteristics, we found that metastasis to the lymph nodes was associated with a significant reduction in the OPRT tumor/normal (T/N) ratio. Our results indicate that it may be possible to predict lymphatic metastasis by determining the T/N ratio for OPRT before surgery.
Ochiai
Takumi
T
Dept. of Surgery, Toubu Chiiki Hospital, Tokyo Metropolitan, Health and Medical Treatment Corporation.
Sugitani
Michiharu
M
Nishimura
Kazuhiko
K
Noguchi
Hajime
H
Watanabe
Tomoo
T
Sengoku
Hironobu
H
Komiyama
Hiromitsu
H
Okano
Masao
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase