PURPOSE: Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) are fluoropyrimidine metabolic enzymes that play important roles in response to chemotherapy in cancer patients. In esophageal cancer, little is known about the relationship between the expression of these enzymes and the corresponding clinicopathologic features.
METHODS: In 72 resected esophageal cancers, TS, DPD, and OPRT expressions were evaluated using immunohistochemistry. Relationships between the enzyme expressions and clinicopathologic features were assessed using Fisher's exact test or chi-square test (categorical variables) or Mann-Whitney rank-sum test (continuous variables). Survival curves were calculated using the Kaplan-Meier method, and the differences were evaluated with log-rank test. Cox proportional hazards model was also used.
RESULTS: High DPD expression was associated with invasion depth, 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) and was associated with decreased patient survival (P = 0.007). In patients receiving adjuvant chemotherapy, low DPD expression did not significantly improve recurrence-free survival. OPRT was expressed especially in esophageal cancer cells as compared to normal squamous cells. High OPRT expression was associated with invasion depth and venous invasion (P = 0.006 and P = 0.003, respectively).
CONCLUSION: In esophageal cancer, DPD expression was associated with tumor progression and prognosis, and OPRT expression correlated with carcinogenesis and tumor progression.
CLINICAL IMPLICATIONS: Further studies to assess the relationships between the expression of DPD or OPRT and chemosensitivity in esophageal cancer patients who received 5-FU containing neoadjuvant chemotherapy are warranted.
DISCLOSURE: Yasuhiro Tsutani, No Financial Disclosure Information; No Product/Research Disclosure Information