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 ' -deo xy-5-fluorouridine (5 ' -DFUR) to 5 ' -fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydroge nase (DPD). We examined the possible correlation of the tissue concentratio ns of both PyNPase and DPD with the clinicopathological features of colorec tal cancer. Methods: In 36 cases of colorectal cancer, the concentrations of both PyNPa se 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 d ifference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metas tasis and vessel invasion (each p < 0.05). On the other hand, the tumor/nor mal 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 re sponse 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 b e 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.