Clinical relevance of the concentrations of both pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer.
BACKGROUND
Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We examined the possible correlation of the tissue concentrations of both PyNPase and DPD with the clinicopathological features of colorectal cancer.


METHODS
In 36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in fresh-frozen samples from either tumor or normal tissue were quantified using ELISA.


RESULTS
The concentration of PyNPase was found to be significantly higher in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metastasis and vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio of DPD was also higher in advanced stage cases and also in the presence of vessel invasion (each p < 0.05), thus indicating a poor response to 5-FU. The PyNPase/DPD ratio, which is known to be correlated with the tissue concentration of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001).


CONCLUSIONS
The tumor/normal tissue ratios of both PyNPase and DPD might be useful candidates for predicting the prognosis of colorectal cancer. The PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue; however, further investigations are needed to clarify the effectiveness of fluoropyrimidine therapy.
Hiroyasu
S
S
First Department of Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. hiroyasu@med.u-ryukyu.ac.jp
Shiraishi
M
M
Samura
H
H
Tokashiki
H
H
Shimoji
H
H
Isa
T
T
Muto
Y
Y
D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D010088:Oxidoreductases / Q000097:blood*; D010430:Pentosyltransferases / Q000097:blood*; D057845:Pyrimidine Phosphorylases; D014407:Tumor Cells, Cultured
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases