Thymidylate Synthase Expression in Stage II and III Colon Cancer

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Abstract
This study is a retrospective analysis of thymidylate synthase (TS) levels in patients with stage II (T3 or T4) and III colon cancer. Two groups of patients were identified: one undergoing surgery alone (98 patients) and the second receiving adjuvant 5-fluorouracil chemotherapy (112 patients). TS analyses were carried out using the 106 monoclonal antibody and a published grading system dividing staining into high and low intensity. The distribution of patients with low versus high TS levels was similar in the two groups. There was no association between TS staining intensity and grade, stage or location of primary. Seventy-nine patients have relapsed: 46 (48%) in the surgery only group, 33 (30%) in the adjuvant therapy group (median follow-up: 51 and 61 months). Similar proportions relapsed when analyzed according to TS: in the surgery only group, 41% of patients with low TS, 48% with high TS; in the adjuvant group, 31% with low TS, 30% with high TS. In the surgery only group, a trend toward improved disease-free survival (DFS) was seen in the low TS group (84 versus 63% at 2 years, p = 0.08). No difference was seen in overall survival. There were no differences in DFS or overall survival in patients receiving adjuvant therapy according to TS intensity. The trend for worse outcome in patients with high TS is consistent with previous reports. The lack of difference in outcome for patients with low and high TS receiving chemotherapy suggests that high TS levels may predict greater benefit from adjuvant treatment.

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