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


OBJECTIVE
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.
Kawai
Ken
K
The Department of Coloproctological Surgery, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Watabe
Suguru
S
Matsuda
Mitsuhiro
M
Sakamoto
Kazuhiro
K
Kamano
Toshiki
T
D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis*; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis
D000964:Antimetabolites, Antineoplastic; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil