Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT) chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT) activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors.While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity.TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT.Advanced colorectal carcinoma remains a significant health care problem in developed countries. Even with complete radical resection, almost half of patients develop local or distant recurrence presumably attributable to disseminated micro metastases present at the time of surgery. Administration of 5-fluorouracil (FU) significantly improves survival in patients with Dukes' C tumors and may also be beneficial in patients with Dukes' B tumors[1]. Nevertheless, a number of patients treated with adjuvant chemotherapy still experience tumor recurrence within 5 years. Identification of highly specific prognostic factors would aid in predicting the efficacy of anticancer agents before the initiation of such therapies.Thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) are key enzymes in the regulation of 5-FU metabolism. TS is the rate-limiting enzyme