Abstract
BckgroundA number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU) metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU.MethodsThis 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.ResultsWhile 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.ConclusionTS 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.
Highlights
MethodsThis 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
We investigated the relationship between clinical pathophysiological characteristics and the activities of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) in 40 patients
Relationship between enzyme activity and clinicopathological variables Age, gender, and pathological findings such as histological type, site and depth of tumor and tumor size except for lymph node metastasis were distributed between the two groups (Table 1)
Summary
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. 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. Patients Forty patients (23 males, 17 females; mean age of 68 ± 7 years) underwent their first colorectal resection at National Kochi Hospital between April 2000 and April 2002. We investigated the relationship between clinical pathophysiological characteristics and the activities of TS, DPD and OPRT in 40 patients. We studied whether the activities of these enzymes were risk factors for recurrence. TS, DPD and OPRT activities were examined in frozen specimens as described by Fujii et al [8] as follows.
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