Correlation between expression of orotate phosphoribosyl transferase and 5-fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer tissue.

Abstract

Background: 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective.

Aim of the study: This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity.

Methods: Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated.

Results: The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group (p < 0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%.

Conclusions: The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy.