CORRELATION BETWEEN CLINICAL PATHOPHYSIOLOGIC FEATURES AND EXPRESSION OF DIHYDROPYRIMIDINE DEHYDROGENASE (DPD), THYMIDYLATE SYNTHASE (TS), AND OROTATE PHOSPHORIBOSYL TRANSFERASE (OPRT) IN HEAD AND NECK CANCER

Abstract

We measured the activity of dihydropyrimidine dehydrogenase (OPD), the amount of thymidylate synthase (TS), and the activity of orotate phosphoribosyl transferase (OPRT) in order to study the contribution of these substances to the effects of the pyrimidine fluoride anticancer drug 5-fluorouracil (5-FU). We also examined the correlation between these three enzymes and clinical pathophysiologic features such as tissue type, extent of tumor invasion, and extent of metastasis to the lymph nodes in 14 head and neck cancer patients. Poorly differentiated squamous cell carcinoma showed significantly higher DPD activity than the other histological type. DPD activity significantly increased as the invasiveness of the tumor increased, and was also higher in patients with lymph nodes metastasis. TS enzyme levels showed a significant correlation with tumor size. OPRT activity showed no significant relationship with the clinical pathophysiologic features. An increase in DPD activity and TS enzyme levels in tumor tissue is a possible cause for the equivocal results of 5-FU based chemotherapy in advanced head and neck squamous cell carcinoma.