The effect of chemotherapy or radiotherapy on thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in cancer of the uterine cervix

Abstract

Levels of 5-FU metabolic or related enzymes, particularly thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), have been investigated in various cancer types, including uterine cervical cancer. Intratumoral TP levels have been reported to increase in response to several chemotherapeutic agents or irradiation in both xenografts and clinical studies. In cervical cancer, however, only a few studies about changes in TP and DPD expression associated with cancer treatment have been published. We evaluated the effect of chemotherapy and/or irradiation on TP and DPD expression in cervical squamous cell carcinoma. Of 27 patients in this study, 12 patients underwent neoadjuvant chemotherapy consisting of nedaplatin, ifosfamide, and/or peplomycin followed by radical surgery, and 15 patients underwent radiotherapy (n=8) or chemoradiotherapy with nedaplatin (n=7) as initial treatment. Tumor specimens were obtained from biopsies acquired before treatment and after administration of chemotherapy (2 weeks after the first and second cycles), and after irradiation with 10 Gy, 20 Gy, and 30 Gy. These specimens were used to measure TP and DPD levels by ELISA. In the 12 patients who received neoadjuvant chemotherapy, intratumoral TP and DPD levels did not change. In contrast, in the 15 patients who underwent radiotherapy or chemoradiotherapy with nedaplatin, TP or DPD expression appeared to be slightly increased or decreased, respectively, after irradiation with 20 Gy, and consequently the TP/DPD ratio was significantly higher after irradiation with 20 Gy than before irradiation. These results suggest a clinical advantage of chemoradiotherapy with capecitabine or doxyfluridine over radiotherapy alone via the elevation of the TP/DPD ratio in cervical squamous cell carcinoma. However, no advantage of combination chemotherapy with these 5-FU derivatives was demonstrated. Therefore, further evaluation with a larger number of patients or with other chemotherapeutic agents is required to confirm these observations.