Thymidine phosphorylase and dihydropyrimidine dehydrogenase activity in colorectal carcinoma and patients prognosis.
OBJECTIVE
5-Fluorouracil (5-FU) is a widely used for colorectal carcinoma. However, the therapeutic effect of 5-FU differs among patients. This difference may be based on the difference in sensitivity of carcinoma cells to 5-FU. The activities of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are reported to be correlated with cancer cell sensitivity against 5-FU in vitro. We evaluated whether TP and DPD are useful markers of tumor sensitivity for 5-FU in colorectal carcinomas.


METHODS
We analyzed the TP and DPD in 189 patients with colorectal carcinoma using an enzyme-linked immunosorbent assay in relation to patients prognosis.


RESULTS
The tumors' mean TP activity was significantly higher than that of noncancerous tissues (100 vs. 47 U/mg protein), but the tumors' mean DPD activity was significantly lower than that of noncancerous tissues (58 vs. 84 U/mg protein). Tumor TP, DPD, and TP/DPD values were not correlated with tumor location or histological types of tumors. Even tumor TP and TP/DPD values in Dukes' stage A tumors were lower than those of other stages; DPD values were not correlated with tumor stages. In 100 patients who underwent intravenous adjuvant 5-FU chemotherapy, prognosis was not correlated with tumor-TP, DPD, or TP/DPD values. Moreover, in 20 patients with synchronous liver metastasis who underwent postoperative 5-FU therapy through the hepatic artery, the survival times of patients was not correlated with tumor-TP, DPD, or TP/DPD values.


CONCLUSIONS
These findings indicate that it is questionable to decide the indication of 5-FU chemotherapy according to tumor TP or DPD status in patients with colorectal cancer.
Ikeguchi
Masahide
M
Division of Operating Room, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan. masaike@grape.med.tottori-u.ac.jp
Makino
Masato
M
Kaibara
Nobuaki
N
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil