Gene Expression of 5-Fluorouracil Metabolic Enzymes in Head and Neck Squamous Cell Carcinomas

Abstract

Objective: To measure the gene expression of the metabolic enzymes of 5 fluorouracil (thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase) to assess the efficacy of 5 fluorouracil inpatients with head and neck cancerPatients and Methods: Tissue specimens of 64 patients with head and neck cancer (41 men and 23 women with a mean age of 62.6 years) who had been surgically treated from April 1997 to March 2004 were included in this study. The mRNA expressions of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase genes were examined from the surgically resected tissues using the Danenberg tumour profile method. The mRNA levels of the 4 enzymes were compared between tumour tissues and adjacent healthy tissues.Results: All specimens showed that thymidylate synthase, thymidine phosphorylase, and orotate phosphoribosyltransferase levels were significantly higher in the primary tumours than in the adjacent healthy tissues, while the levels of dihydropyrimidine dehydrogenase were significantly lower in the primary tumours than in the adjacent healthy tissues.Conclusion: Prediction of the efficacy of 5 fluorouracil therapy in the treatment of head and neck cancer from the measurement of mRNA levels of its metabolic enzymes appears to be feasible and possibly beneficial. Key words: Head and neck neoplasms, Orotate phosphoribosyltransferase, Thymidine phosphorylase, Thymidylate synthase