CONCLUSION: The present study suggested that a high level of thymidine phosphorylase (TP) gene expression is significantly associated with favorable prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. Further studies consisting of large series should be performed to confirm our present results. BACKGROUND: Expression levels of the thymidylate synthase (TS) and 5-FU metabolic enzymes including dihydropyrimidine dehydrogenase (DPD), TP, and orotate phosphoribosyl transferase (OPRT), are reported to be associated with sensitivity to 5-FU-based chemotherapy in several cancers. PATIENTS AND METHODS: Intratumoral mRNA expression levels of TS, DPD, TP, and OPRT in pretreatment biopsy specimens were quantified in 27 patients with advanced oropharyngeal squamous cell carcinomas. Association of these expression levels with response to platinum and 5-FU-based chemotherapy and survival were analyzed statistically. RESULTS: By Spearman's correlation analysis, significant correlation was observed between TS and TP (gamma=0.51, p=0.018). While no correlation was observed between the tumor regression and expression of any of the genes investigated, significant association was observed between prognosis and mRNA expression levels of TS and TP. Multivariate Cox regression analysis revealed that TP mRNA expression level is a significant factor predicting prognosis (hazard ratio (HR) = - 0.204, p=0.043).
CONCLUSION: The present study suggested that a high level of thymidine phosphorylase (TP) gene expression is significantly associated with favorable prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. Further studies consisting of large series should be performed to confirm our present results. BACKGROUND: Expression levels of the thymidylate synthase (TS) and 5-FU metabolic enzymes including dihydropyrimidine dehydrogenase (DPD), TP, and orotate phosphoribosyl transferase (OPRT), are reported to be associated with sensitivity to 5-FU-based chemotherapy in several cancers. PATIENTS AND METHODS: Intratumoral mRNA expression levels of TS, DPD, TP, and OPRT in pretreatment biopsy specimens were quantified in 27 patients with advanced oropharyngeal squamous cell carcinomas. Association of these expression levels with response to platinum and 5-FU-based chemotherapy and survival were analyzed statistically. RESULTS: By Spearman's correlation analysis, significant correlation was observed between TS and TP (gamma=0.51, p=0.018). While no correlation was observed between the tumor regression and expression of any of the genes investigated, significant association was observed between prognosis and mRNA expression levels of TS and TP. Multivariate Cox regression analysis revealed that TP mRNA expression level is a significant factor predicting prognosis (hazard ratio (HR) = - 0.204, p=0.043).