[Clinicopathological significance of orotate phosphoribosyltransferase in gastric carcinoma].

Orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step phosphorylation process of 5-fluorouracil. We have recently developed an ELISA system to measure OPRT levels in cancerous tissues. We examined OPRT levels in 75 gastric carcinoma tissues using this ELISA, and the relationships with clinicopathologic factors were evaluated. A total of 75 surgically-resected gastric carcinoma tissues were subjected to the present study. The intratumoral OPRT level was determined by a newly-developed enzyme-linked immunosorbent assay (ELISA). Enzyme activities of OPRT were also determined using a conventional enzyme assay using radiolabeled 5-fluorouracil as a substrate. OPRT levels in gastric carcinoma tissues measured by ELISA were 5.4+/-3.6 ng/mg protein, ranging from 0.2 to 15.7 ng/mg protein. There was a significant correlation between the OPRT level measured by the ELISA and OPRT enzyme activity (y=0.545x - 0.017, r(2)=0.617, p<0.0001). OPRT levels were significantly higher in patients with differentiated type and invasive type of gastric carcinoma, whereas OPRT levels were not associated with the pathological stage of gastric carcinoma. These results suggest that OPRT levels were related to the histopathological characteristics of gastric carcinoma, and may be related to the response to fluoropyrimidine-based anticancer chemotherapy.