Association of time to recurrence with thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression in stage II and III colorectal cancer.

Patients with International Union Against Cancer (UICC) stage IIb and III colon cancer and stage II and III rectal cancer may receive adjuvant chemotherapy with 5-fluorouracil (5-FU). High levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been associated with resistance to 5-FU in advanced colorectal cancer. The aim of this study was to investigate the association of TS and DPD mRNA levels with recurrence-free survival in patients with colorectal cancer who are receiving adjuvant 5-FU-based chemotherapy. TS and DPD mRNA quantitation was retrospectively performed in primary colorectal cancer specimens from patients receiving adjuvant 5-FU using a reverse transcription- polymerase chain reaction technique. The median TS mRNA level in patients with a recurrence (n = 142) was 0.68, and in patients without a recurrence (n = 206) the median level was 0.80 (P < 0.01). Patients with a recurrence who had a low TS level (TS < or = 0.9; n = 102) had a median recurrence-free survival of 18 months (range 3.0 to 54 months), and those with a high TS level (TS > 0.9; n = 40) had a median recurrence-free survival of 11 months (range 1.7 to 53 months; P = 0.0024). There was no difference in the median recurrence-free survival of patients with low and high DPD mRNA levels. The TS mRNA level may be a useful marker to predict the time to recurrence in patients with colorectal cancer who are receiving adjuvant 5-FU treatment.