Evaluation of sensitivity to 5-FU on the basis of TS and DPD activity in micro tissue specimens

Abstract

651 Background: Preoperative assessment of the anticancer drug sensitivity of tumors plays an important role in the selection of therapy. Evaluation of the 5-FU sensitivity of micro tissue specimens obtained by techniques such as core needle biopsy is often performed before preoperative chemotherapy. The addition of 5-Fluorouracil(F) or its derivatives to AC (EC), the current mainstay of therapy, may further enhance response rate. TS and DPD are used to evaluate the sensitivity and predict the response of tumors to fluoropyrimidine derivatives. Conventional techniques for measuring the activities of these enzymes require large tissue samples, often difficult to obtain before surgery. In contrast, assay of mRNA by PCR permits the use of micro tissue samples obtainable by biopsy. Methods: We measured TS and DPD enzyme activities and mRNA levels in 48 cases of tumor tissue and in the surrounding normal tissue. We also gave 5-FU postoperatively to 107 women with early-stage breast cancer, and divided tissue specimens obtained from these patients into a high-level group and a low-level group to examine the relation to recurrence. Results: TS activities were consistently higher in tumor tissue than in normal tissue, but the difference was not significant (p=0.37, p=0.1454). DPD activity was significantly higher in tumor tissue (p=0.0134), but the DPD mRNA level was higher in normal tissue (p<0.001). The TS activity of tumor tissue correlated with the TS mRNA level (r=0.518, p=0.0017). In contrast, there was no correlation between DPD activity and the DPD mRNA level (r=0.139, p=0.4423). The 5-year disease-free survival rate in patients with low TS activity (68.8%) was significantly better than that in patients with high TS activity (17.9%) (p=0.0018). The 5-year disease-free survival rate did not differ significantly between patients with low DPD activity (50.8%) and those with high DPD activity (66.5%). Conclusions: Our results indicate that TS activity can be used to prognostic factor to 5-FU, even when only micro tumor tissue specimens are available. DPD activity did not correlate with the response to 5-FU. No significant financial relationships to disclose.