Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy

Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradatio n and inactivation of 5-fluorouracil (5-FU). The amount of its expression i n a tumor is thought to be a factor determining the response of the tumor t o 5-FU therapy. We compared DPD activity and DPD mRNA expression in resecte d tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAG) and surgery and a group of 24 patients with advanced ga stric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. I n the surgery alone group, DPD activity decreased significantly as the tumo r stage advanced. This change was not observed in the NAC plus surgery grou p. Neither tumor depth (T factor) nor lymph node metastasis was found to co rrelate with DPD activity. Patients who responded to preoperative chemother apy had lower DPD mRNA levels. Based on these results, we anticipate that m easurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.