Dihydropyrimidine dehydrogenase and orotate phosphoribosyltransferase in esophageal cancer patients: Correlation with clinicopathological factors and prognosis

Abstract

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) are fluoropyrimidine metabolic enzymes which play important roles in the response of cancer patients to chemotherapy. In esophageal cancer, little is known about the relationship between the expression of these enzymes and corresponding clinicopathological features. In the present study, TS, DPD and OPRT expression levels were evaluated in 72 resected esophageal cancer specimens using immunohistochemistry. The relationship between enzyme expression and clinicopathological features was assessed using Fisher's exact test or the χ2 test (categorical variables), or the Mann-Whitney rank-sum test (continuous variables). Survival curves were calculated using the Kaplan-Meier method, and differences evaluated using the log-rank test. The Cox proportional hazards model was also used. High DPD expression was associated with depth of invasion, nodal status, tumor stage, lymphatic invasion and venous invasion (P<0.001, P=0.004, P<0.001, P=0.006, P=0.038, respectively), as well as with decreased patient survival (P=0.007). In patients receiving adjuvant chemotherapy, low DPD expression did not significantly improve recurrence-free survival. OPRT was particularly expressed in esophageal cancer cells as compared to normal squamous cells. High OPRT expression was associated with depth of invasion and venous invasion (P=0.006, P=0.003, respectively). To conclude, in esophageal cancer DPD expression was associated with tumor progression and prognosis, and OPRT expression was correlated with carcinogenesis and tumor progression.